3230 lines
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3230 lines
276 KiB
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Entry
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- *122560 - CORTICOTROPIN-RELEASING HORMONE; CRH
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- OMIM
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<p>
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<span class="h4">*122560</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#history">History</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/122560">Table View</a>
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<a href="#seeAlso"><strong>See Also</strong></a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000147571;t=ENST00000276571" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=1392" class="mim-tip-hint" title="Detailed views of the complete genomes of selected organisms from vertebrates to protozoa." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Genome Viewer', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Genome Viewer</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=122560" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000147571;t=ENST00000276571" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl (MANE Select)</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000756" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000756" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq (MANE)', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq (MANE Select)</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=122560" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=07172&isoform_id=07172_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
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<div><a href="https://www.proteinatlas.org/search/CRH" class="mim-tip-hint" title="The Human Protein Atlas contains information for a large majority of all human protein-coding genes regarding the expression and localization of the corresponding proteins based on both RNA and protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HumanProteinAtlas', 'domain': 'proteinatlas.org'})">Human Protein Atlas</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/protein/35356,117445,4503041,12803539,15029646,30583745,119607303,193786813,957949180,957949183,2462617853,2462617855,2462617858" class="mim-tip-hint" title="NCBI protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Protein', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Protein</a></div>
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<div><a href="https://www.uniprot.org/uniprotkb/P06850" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=1392" class="mim-tip-hint" title="The Gene Portal Hub; customizable portal of gene and protein function information." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'BioGPS', 'domain': 'biogps.org'})">BioGPS</a></div>
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<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000147571;t=ENST00000276571" class="mim-tip-hint" title="Orthologs, paralogs, regulatory regions, and splice variants." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=CRH" class="mim-tip-hint" title="The Human Genome Compendium; web-based cards integrating automatically mined information on human genes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneCards', 'domain': 'genecards.org'})">GeneCards</a></div>
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<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=CRH" class="mim-tip-hint" title="Terms, defined using controlled vocabulary, representing gene product properties (biologic process, cellular component, molecular function) across species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneOntology', 'domain': 'amigo.geneontology.org'})">Gene Ontology</a></div>
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<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+1392" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<dd><a href="http://v1.marrvel.org/search/gene/CRH" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></dd>
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<dd><a href="https://monarchinitiative.org/NCBIGene:1392" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/1392" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr8&hgg_gene=ENST00000276571.5&hgg_start=66176376&hgg_end=66178464&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:2355" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=122560[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=122560[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000147571" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=CRH" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=CRH" class="mim-tip-hint" title="GWAS Central; summary level genotype-to-phenotype information from genetic association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Central', 'domain': 'gwascentral.org'})">GWAS Central </a></div>
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<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=CRH" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=CRH&upstreamSize=0&downstreamSize=0&x=0&y=0" class="mim-tip-hint" title="National Heart, Lung, and Blood Institute Exome Variant Server." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NHLBI EVS', 'domain': 'evs.gs.washington.edu'})">NHLBI EVS</a></div>
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<div><a href="https://www.pharmgkb.org/gene/PA119" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/gene/HGNC:2355" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:88496" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
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<div><a href="http://v1.marrvel.org/search/gene/CRH#HomologGenesPanel" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></div>
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<div><a href="http://www.informatics.jax.org/marker/MGI:88496" class="mim-tip-hint" title="Mouse Genome Informatics; international database resource for the laboratory mouse, including integrated genetic, genomic, and biological data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Gene', 'domain': 'informatics.jax.org'})">MGI Mouse Gene</a></div>
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<div><a href="https://www.mmrrc.org/catalog/StrainCatalogSearchForm.php?search_query=" class="mim-tip-hint" title="Mutant Mouse Resource & Research Centers." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MMRRC', 'domain': 'mmrrc.org'})">MMRRC</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/1392/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=1392" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-041114-75" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:1392" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=CRH&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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122560
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</span>
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</span>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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CORTICOTROPIN-RELEASING HORMONE; CRH
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<div>
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<h4>
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<span class="mim-font">
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CORTICOTROPIN-RELEASING FACTOR; CRF
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</span>
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</h4>
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<div>
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<br />
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=CRH" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">CRH</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/8/313?start=-3&limit=10&highlight=313">8q13.1</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr8:66176376-66178464&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">8:66,176,376-66,178,464</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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<div>
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<br />
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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</span>
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</span>
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</h4>
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<div>
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<a id="cloning" class="mim-anchor"></a>
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<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimCloningToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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<div id="mimCloningFold" class="collapse in mimTextToggleFold">
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<span class="mim-text-font">
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<p>Response to stress in mammals requires an intact hypothalamic-pituitary-adrenal axis. The proximal part of the response is mediated by secretion of corticotropin-releasing hormone (CRH) by the paraventricular nucleus of the hypothalamus. CRH is a 41-amino acid peptide derived by enzymatic cleavage from a 191-amino acid preprohormone. <a href="#24" class="mim-tip-reference" title="Shibahara, S., Morimoto, Y., Furutani, Y., Notake, M., Takahashi, H., Shimizu, S., Horikawa, S., Numa, S. <strong>Isolation and sequence analysis of the human corticotropin-releasing factor precursor gene.</strong> EMBO J. 2: 775-779, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6605851/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6605851</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1983.tb01499.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6605851">Shibahara et al. (1983)</a> cloned and sequenced the human CRH gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6605851" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<a id="mapping" class="mim-anchor"></a>
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<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<div id="mimMappingFold" class="collapse in mimTextToggleFold">
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<span class="mim-text-font">
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<p><a href="#1" class="mim-tip-reference" title="Arbiser, J. L., Morton, C. C., Bruns, G. A. P., Majzoub, J. A. <strong>Human corticotropin releasing hormone gene is located on the long arm of chromosome 8.</strong> Cytogenet. Cell Genet. 47: 113-116, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3259914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3259914</a>] [<a href="https://doi.org/10.1159/000132525" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3259914">Arbiser et al. (1988)</a> assigned the gene for CRH to 8q13 by somatic cell hybrid and in situ hybridization studies. The absence of secondary hybridization strongly suggested that hypothalamic and placental CRH are transcribed from the same gene. <a href="#9" class="mim-tip-reference" title="Kellogg, J., Luty, J. A., Thompson, R., Luo, X. Y., Magenis, R. E., Litt, M. <strong>Corticotropin releasing hormone (CRH) maps to human chromosome 8 and identifies a TaqI RFLP.</strong> Cytogenet. Cell Genet. 51: 1022, 1989."None>Kellogg et al. (1989)</a> corroborated the assignment to 8q13 by in situ hybridization. <a href="#10" class="mim-tip-reference" title="Knapp, L. T., Keegan, C. E., Seasholtz, A. F., Camper, S. A. <strong>Corticotropin-releasing hormone (Crh) maps to mouse chromosome 3.</strong> Mammalian Genome 4: 615-617, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8268662/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8268662</a>] [<a href="https://doi.org/10.1007/BF00361396" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8268662">Knapp et al. (1993)</a> showed that the homologous gene is located on mouse chromosome 3. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8268662+3259914" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<br />
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<div>
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<p><a href="#21" class="mim-tip-reference" title="Sasaki, A., Shinkawa, O., Margioris, A. N., Liotta, A. S., Sato, S., Murakami, O., Go, M., Shimizu, Y., Hanew, K., Yoshinaga, K. <strong>Immunoreactive corticotropin-releasing hormone in human plasma during pregnancy, labor, and delivery.</strong> J. Clin. Endocr. Metab. 64: 224-229, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3491832/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3491832</a>] [<a href="https://doi.org/10.1210/jcem-64-2-224" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3491832">Sasaki et al. (1987)</a> measured plasma CRH levels during pregnancy, labor, and delivery, and at 1 and 2 hours postpartum in 97 pregnant women. Plasma CRH concentrations progressively increased during pregnancy, correlated well with the weeks of pregnancy, and declined rapidly after delivery. Umbilical cord CRH levels were much lower than those in corresponding maternal plasma, suggesting that CRH is preferentially secreted into the maternal circulation. Maternal plasma CRH-sized material, obtained by affinity chromatography and gel filtration, stimulated ACTH release from anterior pituitary tissue in a dose-dependent manner and was equipotent with rat CRH. <a href="#21" class="mim-tip-reference" title="Sasaki, A., Shinkawa, O., Margioris, A. N., Liotta, A. S., Sato, S., Murakami, O., Go, M., Shimizu, Y., Hanew, K., Yoshinaga, K. <strong>Immunoreactive corticotropin-releasing hormone in human plasma during pregnancy, labor, and delivery.</strong> J. Clin. Endocr. Metab. 64: 224-229, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3491832/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3491832</a>] [<a href="https://doi.org/10.1210/jcem-64-2-224" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3491832">Sasaki et al. (1987)</a> suggested that placental CRH might be an important stimulator of the maternal pituitary-adrenal axis during pregnancy, labor, and delivery. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3491832" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Campbell, E. A., Linton, E. A., Wolfe, C. D. A., Scraggs, P. R., Jones, M. T., Lowry, P. J. <strong>Plasma corticotropin-releasing hormone concentrations during pregnancy and parturition.</strong> J. Clin. Endocr. Metab. 64: 1054-1059, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3494036/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3494036</a>] [<a href="https://doi.org/10.1210/jcem-64-5-1054" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3494036">Campbell et al. (1987)</a> measured plasma CRH levels throughout the third trimester of pregnancy, during labor, and postpartum in 80 normal pregnant women and 49 women with pregnancy-induced hypertension (PIH; see PEE1, <a href="/entry/189800">189800</a>). In normal pregnant women, plasma CRH levels increased markedly at 40 weeks and remained so during labor. Women with PIH had plasma CRH levels significantly elevated above that normal range, as did 11 women from the 'normal' group who subsequently went into premature labor. After delivery, plasma CRH returned to normal within 15 hours. Total plasma cortisol levels varied little throughout the third trimester, but increased during labor and remained elevated for 2 to 3 days postpartum. There was, therefore, no correlation between plasma cortisol and CRH, implying that placental CRH is not primarily involved in the control of the maternal hypothalamopituitary adrenal axis during pregnancy. <a href="#4" class="mim-tip-reference" title="Campbell, E. A., Linton, E. A., Wolfe, C. D. A., Scraggs, P. R., Jones, M. T., Lowry, P. J. <strong>Plasma corticotropin-releasing hormone concentrations during pregnancy and parturition.</strong> J. Clin. Endocr. Metab. 64: 1054-1059, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3494036/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3494036</a>] [<a href="https://doi.org/10.1210/jcem-64-5-1054" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3494036">Campbell et al. (1987)</a> also noted that concentrations of CRH in umbilical cord plasma samples were considerably lower than those in the maternal circulation and were close to those in normal nonpregnant adults. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3494036" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#19" class="mim-tip-reference" title="Robinson, B. G., Emanuel, R. L., Frim, D. M., Majzoub, J. A. <strong>Glucocorticoid stimulates expression of corticotropin-releasing hormone gene in human placenta.</strong> Proc. Nat. Acad. Sci. 85: 5244-5248, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2839838/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2839838</a>] [<a href="https://doi.org/10.1073/pnas.85.14.5244" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2839838">Robinson et al. (1988)</a> established primary cultures of purified human cytotrophoblasts to examine the effect of glucocorticoids on the expression of the CRH gene in placenta. The authors found that glucocorticoids stimulate synthesis of placental CRH, as demonstrated by slot blot hybridization of RNA prepared from cytotrophoblasts. In addition, using the technique of RNase H digestion of a heteroduplex between CRH mRNA and a synthetic oligonucleotide complementary to the 5-prime CRH mRNA, the authors demonstrated the transcriptional initiation site of the CRH gene. The authors speculated on the role of this regulatory mechanism on the levels of fetal glucocorticoids in the pre- and postparturition periods. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2839838" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>CRH is made not only in the hypothalamus but also in peripheral tissues, such as T lymphocytes, and is expressed in very large amounts in the human placenta (<a href="#19" class="mim-tip-reference" title="Robinson, B. G., Emanuel, R. L., Frim, D. M., Majzoub, J. A. <strong>Glucocorticoid stimulates expression of corticotropin-releasing hormone gene in human placenta.</strong> Proc. Nat. Acad. Sci. 85: 5244-5248, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2839838/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2839838</a>] [<a href="https://doi.org/10.1073/pnas.85.14.5244" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2839838">Robinson et al., 1988</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2839838" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="McLean, M., Bisits, A., Davies, J., Woods, R., Lowry, P., Smith, R. <strong>A placental clock controlling the length of human pregnancy.</strong> Nature Med. 1: 460-463, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7585095/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7585095</a>] [<a href="https://doi.org/10.1038/nm0595-460" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7585095">McLean et al. (1995)</a> presented evidence that placental secretion of CRH is a marker of the 'placental clock' that is active from an early stage in human pregnancy and determines the length of gestation and the timing of parturition and delivery. Using a prospective, longitudinal cohort study of 485 pregnant women, <a href="#17" class="mim-tip-reference" title="McLean, M., Bisits, A., Davies, J., Woods, R., Lowry, P., Smith, R. <strong>A placental clock controlling the length of human pregnancy.</strong> Nature Med. 1: 460-463, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7585095/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7585095</a>] [<a href="https://doi.org/10.1038/nm0595-460" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7585095">McLean et al. (1995)</a> demonstrated that placental secretion of CRH, measured as maternal plasma CRH concentration as early as 16 to 20 weeks of gestation, identified groups of women destined to experience normal term, preterm, or post-term delivery. An exponential rise in maternal plasma CRH concentrations with advancing pregnancy is associated with a concomitant fall in concentrations of the specific CRH-binding protein (CRHBP; <a href="/entry/122559">122559</a>) in late pregnancy, leading to a rapid increase in circulating levels of bioavailable CRH at the onset of parturition, suggesting that CRH may act directly as a trigger for parturition in humans. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7585095" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Behan, D. P., Heinrichs, S. C., Troncoso, J. C., Liu, X.-J., Kawas, C. H., Ling, N., De Souza, E. B. <strong>Displacement of corticotropin releasing factor from its binding protein as a possible treatment for Alzheimer's disease.</strong> Nature 378: 284-287, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7477348/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7477348</a>] [<a href="https://doi.org/10.1038/378284a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7477348">Behan et al. (1995)</a> observed that the marked reduction in CRF found in Alzheimer disease (AD; e.g., <a href="/entry/104300">104300</a>) is due to CRFBP (CRHBP; <a href="/entry/122559">122559</a>), a high-affinity binding protein that inactivates CRF. The authors showed that ligands which interfere with this process in AD raise free CRF levels to that of controls. <a href="#3" class="mim-tip-reference" title="Behan, D. P., Heinrichs, S. C., Troncoso, J. C., Liu, X.-J., Kawas, C. H., Ling, N., De Souza, E. B. <strong>Displacement of corticotropin releasing factor from its binding protein as a possible treatment for Alzheimer's disease.</strong> Nature 378: 284-287, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7477348/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7477348</a>] [<a href="https://doi.org/10.1038/378284a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7477348">Behan et al. (1995)</a> also studied the learning and memory effects of a CRF-receptor agonist and a CRFBP ligand in rats. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7477348" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Asakura, H., Zwain, I. H., Yen, S. S. C. <strong>Expression of genes encoding corticotropin-releasing factor (CRF), type 1 CRF receptor, and CRF-binding protein and localization of the gene products in the human ovary.</strong> J. Clin. Endocr. Metab. 82: 2720-2725, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9253360/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9253360</a>] [<a href="https://doi.org/10.1210/jcem.82.8.4119" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9253360">Asakura et al. (1997)</a> localized immunoreactive corticotropin-releasing factor (IrCRF) and its mRNA to the thecal cells of small antral and mature follicles of the human ovary. A low abundance of IrCRF and mRNA was also detected in stromal cells of both stages of follicles. Greater CRF gene expression was seen in mature than in small antral follicles. CRF receptor (CRFR1; <a href="/entry/122561">122561</a>) mRNA signal was found exclusively in thecal cells of mature follicles and moderately in small antral follicles. Granulosa cells were devoid of CRF and CRFR1 mRNAs and proteins. The authors concluded that the thecal compartment of the human ovary contains a CRF system endowed with CRF, CRFR1, and the CRFBP protein while granulosa cells are devoid of this system. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9253360" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In choriocarcinoma cell lines, activation of cAMP-dependent pathways increases human CRH reporter gene expression. <a href="#23" class="mim-tip-reference" title="Scatena, C. D., Adler, S. <strong>Characterization of a human-specific regulator of placental corticotropin-releasing hormone.</strong> Molec. Endocr. 12: 1228-1240, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9717848/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9717848</a>] [<a href="https://doi.org/10.1210/mend.12.8.0150" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9717848">Scatena and Adler (1998)</a> identified a cAMP-responsive region between -200 and -99 bp of the CRH promoter, distinct from the cAMP response element (CRE) at -220 bp, and also identified a candidate transcription factor present in nuclear extracts of human, but not rodent, choriocarcinoma cell lines. This region, which does not contain a canonical CRE, transfers protein kinase A (<a href="https://enzyme.expasy.org/EC/2.7.1.37" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 2.7.1.37</a>; see <a href="/entry/176911">176911</a>) responsiveness to a heterologous promoter. Using electromobility shift assays and methylation and uracil interference studies, <a href="#23" class="mim-tip-reference" title="Scatena, C. D., Adler, S. <strong>Characterization of a human-specific regulator of placental corticotropin-releasing hormone.</strong> Molec. Endocr. 12: 1228-1240, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9717848/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9717848</a>] [<a href="https://doi.org/10.1210/mend.12.8.0150" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9717848">Scatena and Adler (1998)</a> localized factor binding to a 20-bp region from -128 to -109 bp of the CRH promoter. This 20-bp fragment exhibited a similar shift in nuclear extracts from both human term placenta and from human JEG-3 cells. Although this factor participates in cAMP-regulated gene expression, competition electrophoretic mobility assays demonstrated that the factor does not bind to a CRE. Furthermore, neither anti-CREB (<a href="/entry/123810">123810</a>) nor anti-ATF2 (<a href="/entry/123811">123811</a>) antibodies altered factor binding. The authors concluded that this 58-kD protein is the human-specific CRH activator previously identified (<a href="#22" class="mim-tip-reference" title="Scatena, C. D., Adler, S. <strong>Trans-acting factors dictate the species-specific placental expression of corticotropin-releasing factor genes in choriocarcinoma cell lines.</strong> Endocrinology 137: 3000-3008, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8770924/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8770924</a>] [<a href="https://doi.org/10.1210/endo.137.7.8770924" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8770924">Scatena and Adler, 1996</a>) as contributing to the species-specific expression of CRH in human placenta. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9717848+8770924" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#26" class="mim-tip-reference" title="Xu, B., Sano, T., Yamada, S., Li, C. C., Hirokawa, M. <strong>Expression of corticotropin-releasing hormone messenger ribonucleic acid in human pituitary corticotroph adenomas associated with proliferative potential.</strong> J. Clin. Endocr. Metab. 85: 1220-1225, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10720066/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10720066</a>] [<a href="https://doi.org/10.1210/jcem.85.3.6471" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10720066">Xu et al. (2000)</a> investigated the effects of CRH expression in human pituitary corticotroph adenomas (PCAs). CRH mRNA transcripts were demonstrated on paraffin sections using the quantitative in situ hybridization method in 37 of 43 PCAs, including 17 of 22 microadenomas, 15 of 15 macroadenomas, and 5 of 6 locally invasive adenomas according to Hardy's classification of pituitary adenomas. The more important findings were that CRH mRNA signal intensity in pituitary corticotroph adenoma cells was linearly correlated with Ki-67 (<a href="/entry/176741">176741</a>) tumor growth fractions, and in macroadenoma and locally invasive adenoma cells it was significantly higher than in microadenoma cells. On the other hand, CRH mRNA transcript accumulation was absent or negligible in 10 normal pituitary glands. The authors concluded that CRH from a local source of corticotroph adenoma cells not only has autocrine/paracrine functions in corticotroph adenomatous tissue, but also is an important factor associated with a proliferative potential of PCAs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10720066" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Cheng, Y.-H., Nicholson, R. C., King, B., Chan, E.-C., Fitter, J. T., Smith, R. <strong>Corticotropin-releasing hormone gene expression in primary placental cells is modulated by cyclic adenosine 3-prime,5-prime-monophosphate.</strong> J. Clin. Endocr. Metab. 85: 1239-1244, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10720069/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10720069</a>] [<a href="https://doi.org/10.1210/jcem.85.3.6420" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10720069">Cheng et al. (2000)</a> explored the effect of cAMP on CRH promoter activity in primary cultures of human placental cells. Both forskolin and 8-bromo-cAMP, activators of protein kinase A, can increase CRH promoter activity 5-fold in transiently transfected human primary placental cells, in a manner that parallels the increase in endogenous CRH peptide. Electrophoretic mobility shift assay and mutation analysis combined with transient transfection demonstrated that in placental cells cAMP stimulates CRH gene expression through a cAMP regulatory element in the proximal CRH promoter region and involves a placental nuclear protein interacting specifically with the cAMP regulatory element. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10720069" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>It has been suggested that CRH is a placental clock that controls the duration of pregnancy and that the timing of the rise in CRH may permit prediction of the onset of labor. <a href="#8" class="mim-tip-reference" title="Inder, W. J., Prickett, T. C. R., Ellis, M. J., Hull, L., Reid, R., Benny, P. S., Livesey, J. H., Donald, R. A. <strong>The utility of plasma CRH as a predictor of preterm delivery.</strong> J. Clin. Endocr. Metab. 86: 5706-5710, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11739425/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11739425</a>] [<a href="https://doi.org/10.1210/jcem.86.12.8080" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11739425">Inder et al. (2001)</a> performed a prospective longitudinal study, in 297 women, to examine the utility of a single second-trimester plasma CRH measurement to predict preterm delivery. Sampling for plasma CRH at 26 weeks' gestation seemed the optimal time point to maximize sensitivity and specificity of the test. The mean (+/- SD) plasma CRH in women at this gestation who eventually delivered after spontaneous labor within 1 week of their due date (39 to 41 weeks, n = 127) was 34.7 +/- 27.0 pM. A plasma CRH of more than 90 pM at 26 weeks' gestation had a sensitivity of 45% and a specificity of 94% for prediction of preterm delivery. The authors concluded that a single measurement of plasma CRH, toward the end of the second trimester, may identify a group at risk for preterm delivery, but over 50% of such deliveries will be unpredicted. These data do not support the routine clinical use of plasma CRH as a predictor of preterm labor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11739425" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Makrigiannakis, A., Zoumakis, E., Kalantaridou, S., Coutifaris, C., Margioris, A. N., Coukos, G., Rice, K. C., Gravanis, A., Chrousos, G. P. <strong>Corticotropin-releasing hormone promotes blastocyst implantation and early maternal tolerance.</strong> Nature Immun. 2: 1018-1024, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11590404/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11590404</a>] [<a href="https://doi.org/10.1038/ni719" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11590404">Makrigiannakis et al. (2001)</a> observed decreased FASL expression in human extravillous trophoblasts and choriocarcinoma cell lines following treatment with the CRHR1 antagonist antalarmin. In contrast, CRH increased FASL expression and induced apoptosis of activated T cells, and antalarmin inhibited this effect. Treatment of female rats with antalarmin resulted in a marked decrease in implantation sites and live embryos, as well as diminished endometrial Fasl expression. Embryos from T cell-deficient mothers or from syngeneic matings were not rejected when mothers were given antalarmin. <a href="#15" class="mim-tip-reference" title="Makrigiannakis, A., Zoumakis, E., Kalantaridou, S., Coutifaris, C., Margioris, A. N., Coukos, G., Rice, K. C., Gravanis, A., Chrousos, G. P. <strong>Corticotropin-releasing hormone promotes blastocyst implantation and early maternal tolerance.</strong> Nature Immun. 2: 1018-1024, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11590404/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11590404</a>] [<a href="https://doi.org/10.1038/ni719" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11590404">Makrigiannakis et al. (2001)</a> proposed that locally produced CRH promotes implantation and the maintenance of early pregnancy by killing activated T cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11590404" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Sebaceous glands may be involved in a pathway conceptually similar to that of the hypothalamic-pituitary-adrenal (HPA) axis. CRH is the most proximal element of the HPA axis, and it acts as a central coordinator for neuroendocrine and behavioral responses to stress. To examine the probability of an HPA equivalent pathway in sebaceous glands, <a href="#27" class="mim-tip-reference" title="Zouboulis, C. C., Seltmann, H., Hiroi, N., Chen, W., Young, M., Oeff, M., Scherbaum, W. A., Orfanos, C. E., McCann, S. M., Bornstein, S. R. <strong>Corticotropin-releasing hormone: an autocrine hormone that promotes lipogenesis in human sebocytes.</strong> Proc. Nat. Acad. Sci. 99: 7148-7153, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12011471/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12011471</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12011471[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.102180999" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12011471">Zouboulis et al. (2002)</a> investigated the expression of CRH, CRH-binding protein, CRHBP (<a href="/entry/122559">122559</a>), and CRH receptors (CRHR1, <a href="/entry/122561">122561</a> and CRHR2, <a href="/entry/602034">602034</a>) in sebocytes in vitro and their regulation by CRH and several other hormones. CRHR1 was the predominant type, being twice as abundant as CRHR2. CRH was biologically active on human sebocytes; it induced biphasic increase in synthesis of sebaceous lipids, although it did not affect cell viability, cell proliferation, or IL1B (<a href="/entry/147720">147720</a>)-induced IL8 (<a href="/entry/146930">146930</a>) release. <a href="#27" class="mim-tip-reference" title="Zouboulis, C. C., Seltmann, H., Hiroi, N., Chen, W., Young, M., Oeff, M., Scherbaum, W. A., Orfanos, C. E., McCann, S. M., Bornstein, S. R. <strong>Corticotropin-releasing hormone: an autocrine hormone that promotes lipogenesis in human sebocytes.</strong> Proc. Nat. Acad. Sci. 99: 7148-7153, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12011471/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12011471</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12011471[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.102180999" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12011471">Zouboulis et al. (2002)</a> interpreted these and other findings as indicating that CRH may be an autocrine hormone for human sebocytes that exerts homeostatic lipogenic activity, whereas testosterone and growth hormone induced CRH negative feedback. The findings implicated CRH in the clinical development of acne, seborrhea, androgenetic alopecia, skin aging, xerosis, and other skin disorders associated with alterations in lipid formation of sebaceous origin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12011471" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Maji, S. K., Perrin, M. H., Sawaya, M. R., Jessberger, S., Vadodaria, K., Rissman, R. A., Singru, P. S., Nilsson, K. P. R., Simon, R., Schubert, D., Eisenberg, D., Rivier, J., Sawchenko, P., Vale, W., Riek, R. <strong>Functional amyloids as natural storage of peptide hormones in pituitary secretory granules.</strong> Science 325: 328-332, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19541956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19541956</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19541956[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1173155" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19541956">Maji et al. (2009)</a> found that peptide and protein hormones, including CRF, in secretory granules of the endocrine system are stored in an amyloid-like cross-beta-sheet-rich conformation, and concluded that functional amyloids in the pituitary and other organs can contribute to normal cell and tissue physiology. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19541956" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Lemos, J. C., Wanat, M. J., Smith, J. S., Reyes, B. A. S., Hollon, N. G., Van Bockstaele, E. J., Chavkin, C., Phillips, P. E. M. <strong>Severe stress switches CRF action in the nucleus accumbens from appetitive to aversive.</strong> Nature 490: 402-406, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22992525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22992525</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22992525[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature11436" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22992525">Lemos et al. (2012)</a> reported that CRF, a neuropeptide released in response to acute stressors and other arousing environmental stimuli, acts in the nucleus accumbens of naive mice to increase dopamine release through coactivation of the receptors CRFR1 and CRFR2. Remarkably, severe-stress exposure completely abolished this effect without recovery for at least 90 days. This loss of CRF's capacity to regulate dopamine release in the nucleus accumbens is accompanied by a switch in the reaction to CRF from appetitive to aversive, indicating a diametric change in the emotional response to acute stressors. <a href="#12" class="mim-tip-reference" title="Lemos, J. C., Wanat, M. J., Smith, J. S., Reyes, B. A. S., Hollon, N. G., Van Bockstaele, E. J., Chavkin, C., Phillips, P. E. M. <strong>Severe stress switches CRF action in the nucleus accumbens from appetitive to aversive.</strong> Nature 490: 402-406, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22992525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22992525</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22992525[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature11436" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22992525">Lemos et al. (2012)</a> concluded that their results offer a biologic substrate for the switch in affect which is central to stress-induced depressive disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22992525" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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For a discussion of a possible association between autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE; see <a href="/entry/600513">600513</a>) and variation in the CRH gene, see <a href="#0001">122560.0001</a>.</p>
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<p>To find the importance of CRH in the response of the hypothalamic-pituitary-adrenal axis to stress and its role in fetal development, <a href="#18" class="mim-tip-reference" title="Muglia, L., Jacobson, L., Dikkes, P., Majzoub, J. A. <strong>Corticotropin-releasing hormone deficiency reveals major fetal but not adult glucocorticoid need.</strong> Nature 373: 427-432, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7830793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7830793</a>] [<a href="https://doi.org/10.1038/373427a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7830793">Muglia et al. (1995)</a> constructed a mouse model of CRH deficiency by targeted mutation in embryonic stem cells. They reported that CRH-deficient mice reveal a fetal glucocorticoid requirement for lung maturation. Postnatally, however, despite marked glucocorticoid deficiency, the mice exhibited normal growth, fertility, and longevity, suggesting that the major role of glucocorticoid occurs during fetal, rather than postnatal, life. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7830793" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In adult male rhesus macaques, <a href="#7" class="mim-tip-reference" title="Habib, K. E., Weld, K. P., Rice, K. C., Pushkas, J., Champoux, M., Listwak, S., Webster, E. L., Atkinson, A. J., Schulkin, J., Contoreggi, C., Chrousos, G. P., McCann, S. M., Suomi, S. J., Higley, J. D., Gold, P. W. <strong>Oral administration of a corticotropin-releasing hormone receptor antagonist significantly attenuates behavioral, neuroendocrine, and autonomic responses to stress in primates.</strong> Proc. Nat. Acad. Sci. 97: 6079-6084, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10823952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10823952</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10823952[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.97.11.6079" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10823952">Habib et al. (2000)</a> evaluated the effects of a lipophilic nonpeptide antagonist to CRH type 1 receptor, antalarmin, on the behavioral, neuroendocrine, and autonomic components of the stress response. After oral administration, significant antalarmin concentrations were detected in the systemic circulation and the cerebrospinal fluid. The monkeys were exposed to an intense social stressor, namely, placement of 2 unfamiliar males in adjacent cages separated only by a transparent Plexiglas screen. Antalarmin significantly inhibited a repertoire of behaviors associated with anxiety and fear, such as body tremors, grimacing, teeth gnashing, urination, and defecation. In contrast, antalarmin increased exploratory and sexual behaviors that are normally suppressed during stress. Moreover, antalarmin significantly diminished the increases in cerebrospinal fluid CRH as well as the pituitary-adrenal, sympathetic, and adrenal medullary responses to stress. <a href="#7" class="mim-tip-reference" title="Habib, K. E., Weld, K. P., Rice, K. C., Pushkas, J., Champoux, M., Listwak, S., Webster, E. L., Atkinson, A. J., Schulkin, J., Contoreggi, C., Chrousos, G. P., McCann, S. M., Suomi, S. J., Higley, J. D., Gold, P. W. <strong>Oral administration of a corticotropin-releasing hormone receptor antagonist significantly attenuates behavioral, neuroendocrine, and autonomic responses to stress in primates.</strong> Proc. Nat. Acad. Sci. 97: 6079-6084, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10823952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10823952</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10823952[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.97.11.6079" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10823952">Habib et al. (2000)</a> suggested that a CRH type 1 receptor antagonist may be of therapeutic value in human psychiatric, reproductive, and cardiovascular disorders associated with CRH system hyperactivity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10823952" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using a turpentine-induced model of subacute inflammation in Crh -/- mice, <a href="#25" class="mim-tip-reference" title="Venihaki, M., Dikkes, P., Carrigan, A., Karalis, K. P. <strong>Corticotropin-releasing hormone regulates IL-6 expression during inflammation.</strong> J. Clin. Invest. 108: 1159-1166, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11602623/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11602623</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11602623[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI12869" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11602623">Venihaki et al. (2001)</a> demonstrated that during inflammation Crh is required for a normal adrenocorticotropin hormone (ACTH) increase but not for adrenal corticosterone rise. A paradoxical increase of plasma interleukin-6 (IL6; <a href="/entry/147620">147620</a>) associated with Crh deficiency suggested that regulation of Il6 release during inflammation is Crh dependent. <a href="#25" class="mim-tip-reference" title="Venihaki, M., Dikkes, P., Carrigan, A., Karalis, K. P. <strong>Corticotropin-releasing hormone regulates IL-6 expression during inflammation.</strong> J. Clin. Invest. 108: 1159-1166, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11602623/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11602623</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11602623[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI12869" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11602623">Venihaki et al. (2001)</a> also demonstrated that adrenal Il6 expression is Crh dependent, as its basal and inflammation-induced expression was blocked by Crh deficiency. Mice deficient in both Crh and Il6 had a flat hypothalamic-pituitary-adrenal response to inflammation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11602623" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Donelan, J., Boucher, W., Papadopoulou, N., Lytinas, M., Papaliodis, D., Dobner, P., Theoharides, T. C. <strong>Corticotropin-releasing hormone induces skin vascular permeability through a neurotensin-dependent process.</strong> Proc. Nat. Acad. Sci. 103: 7759-7764, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16682628/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16682628</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16682628[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0602210103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16682628">Donelan et al. (2006)</a> used intradermal injection of various peptides to assess vascular permeability, as measured by Evans blue extravasation, in rat skin. They found that Crh and neurotensin (NTS; <a href="/entry/162650">162650</a>) potently induced vascular permeability. The effect of Crh and Nts was blocked by a neurotensin receptor (see NTSR1; <a href="/entry/162651">162651</a>) antagonist and did not occur in Nts -/- mice. RT-PCR analysis showed that Crh and Nts were present in dorsal root ganglia and that Crhr was expressed on mouse skin mast cells. <a href="#6" class="mim-tip-reference" title="Donelan, J., Boucher, W., Papadopoulou, N., Lytinas, M., Papaliodis, D., Dobner, P., Theoharides, T. C. <strong>Corticotropin-releasing hormone induces skin vascular permeability through a neurotensin-dependent process.</strong> Proc. Nat. Acad. Sci. 103: 7759-7764, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16682628/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16682628</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16682628[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0602210103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16682628">Donelan et al. (2006)</a> concluded that NTS is involved in the action of CRH. They suggested that mast cell-neuron interactions and mast cell activation may be involved in the pathophysiology of skin conditions such as atopic dermatitis, urticaria, and psoriasis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16682628" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a consanguineous kindred in Israel, <a href="#16" class="mim-tip-reference" title="Mandel, H., Berant, M., Gotfried, E., Hochberg, Z. <strong>Autosomal recessive hypothalamic corticotropin deficiency: a new entity and its metabolic consequences. (Abstract)</strong> Am. J. Hum. Genet. 47 (suppl.): A66, 1990."None>Mandel et al. (1990)</a> identified 11 children with autosomal recessive hypothalamic corticotropin deficiency. Death without diagnosis occurred in 7. Four of the affected children were studied extensively; 2 were diagnosed prenatally. The first diagnosed patient presented at age 2 months with hypoglycemia, hepatitis, facial dysmorphism, convulsions, and agenesis of the corpus callosum. The prenatal diagnosis was suggested by low maternal urinary estriol and confirmed at birth by undetectable levels of cortisol and ACTH (<a href="/entry/176830">176830</a>). Treatment with cortisol resulted in normal development. Growth hormone deficiency and a thyroid organification defect were secondary to adrenal insufficiency. The disorder was clearly an autosomal recessive. <a href="#14" class="mim-tip-reference" title="Majzoub, J. A. <strong>Personal Communication.</strong> Boston, Mass. 3/3/1995."None>Majzoub (1995)</a> stated that the findings in this Bedouin family had not been reported in full. Linkage was being used to determine whether CRH deficiency was indeed present.</p>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>1 Selected Example</a>):</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=122560[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs748404250 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs748404250;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs748404250?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs748404250" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs748404250" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000172993 OR RCV000192059 OR RCV004019949" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000172993, RCV000192059, RCV004019949" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000172993...</a>
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<p>This variant is classified as a variant of unknown significance because its contribution to autosomal dominant nocturnal frontal lobe epilepsy (see ENFL1, <a href="/entry/600513">600513</a>) has not been confirmed.</p><p>In 2 Italian sibs with autosomal dominant nocturnal frontal lobe epilepsy, <a href="#20" class="mim-tip-reference" title="Sansoni, V., Forcella, M., Mozzi, A., Fusi, P., Ambrosini, R., Ferini-Strambi, L., Combi, R. <strong>Functional characterization of a CRH missense mutation identified in an ADNFLE family.</strong> PLoS One 8: e61306, 2013. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23593457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23593457</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23593457[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1371/journal.pone.0061306" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23593457">Sansoni et al. (2013)</a> identified a heterozygous c.89C-G transversion (c.89C-G, NM_000756.2) in exon 2 of the CRH gene, resulting in a pro30-to-arg (P30R) substitution at a highly conserved residue in the pro-sequence of the protein. The variant was not found in 100 ancestry-matched controls or in public databases. In vitro functional expression studies in neural cells showed that the variant resulted in a lower level of the CRH precursor protein within the cell and slower excretion of the mature hormone. The variant protein showed higher colocalization in the Golgi apparatus compared to wildtype. The findings suggested that the variant resulted in a delay in posttranslational protein processing, leading to degradation and/or slower release of the mature peptide. The released mature protein encoded by the variant was identical to the wildtype protein, since the variant is cleaved from the precursor intracellullarly. <a href="#20" class="mim-tip-reference" title="Sansoni, V., Forcella, M., Mozzi, A., Fusi, P., Ambrosini, R., Ferini-Strambi, L., Combi, R. <strong>Functional characterization of a CRH missense mutation identified in an ADNFLE family.</strong> PLoS One 8: e61306, 2013. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23593457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23593457</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23593457[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1371/journal.pone.0061306" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23593457">Sansoni et al. (2013)</a> postulated that the mutation impairs prompt release of the hormone and alters immediate response to stress agents. The patients had onset of nocturnal motor episodes at ages 10 and 11 years, respectively. The episodes occurred almost nightly at first, and were characterized by sudden elevation of the head and trunk, often associated with manual and pedal motor activity. Frequency of episodes in 1 patient decreased in her late twenties. The deceased father reportedly had REM sleep behavior disorder, but his DNA was not available. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23593457" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<h4 href="#mimSeeAlsoFold" id="mimSeeAlsoToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<a href="#Kyllo1996" class="mim-tip-reference" title="Kyllo, J. H., Collins, M. M., Vetter, K. L., Cuttler, L., Rosenfield, R. L., Donohoue, P. A. <strong>Linkage of congenital isolated adrenocorticotropic hormone deficiency to the corticotropin releasing hormone locus using simple sequence repeat polymorphisms.</strong> Am. J. Med. Genet. 62: 262-267, 1996.">Kyllo et al. (1996)</a>
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<strong>REFERENCES</strong>
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<a id="1" class="mim-anchor"></a>
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<a id="Arbiser1988" class="mim-anchor"></a>
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Arbiser, J. L., Morton, C. C., Bruns, G. A. P., Majzoub, J. A.
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<strong>Human corticotropin releasing hormone gene is located on the long arm of chromosome 8.</strong>
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Cytogenet. Cell Genet. 47: 113-116, 1988.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3259914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3259914</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3259914" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1159/000132525" target="_blank">Full Text</a>]
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<a id="Asakura1997" class="mim-anchor"></a>
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Asakura, H., Zwain, I. H., Yen, S. S. C.
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<strong>Expression of genes encoding corticotropin-releasing factor (CRF), type 1 CRF receptor, and CRF-binding protein and localization of the gene products in the human ovary.</strong>
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J. Clin. Endocr. Metab. 82: 2720-2725, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9253360/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9253360</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9253360" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1210/jcem.82.8.4119" target="_blank">Full Text</a>]
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<a id="Behan1995" class="mim-anchor"></a>
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Behan, D. P., Heinrichs, S. C., Troncoso, J. C., Liu, X.-J., Kawas, C. H., Ling, N., De Souza, E. B.
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<strong>Displacement of corticotropin releasing factor from its binding protein as a possible treatment for Alzheimer's disease.</strong>
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Nature 378: 284-287, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7477348/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7477348</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7477348" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/378284a0" target="_blank">Full Text</a>]
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Campbell, E. A., Linton, E. A., Wolfe, C. D. A., Scraggs, P. R., Jones, M. T., Lowry, P. J.
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<strong>Plasma corticotropin-releasing hormone concentrations during pregnancy and parturition.</strong>
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J. Clin. Endocr. Metab. 64: 1054-1059, 1987.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3494036/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3494036</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3494036" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1210/jcem-64-5-1054" target="_blank">Full Text</a>]
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<a id="Cheng2000" class="mim-anchor"></a>
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Cheng, Y.-H., Nicholson, R. C., King, B., Chan, E.-C., Fitter, J. T., Smith, R.
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<strong>Corticotropin-releasing hormone gene expression in primary placental cells is modulated by cyclic adenosine 3-prime,5-prime-monophosphate.</strong>
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J. Clin. Endocr. Metab. 85: 1239-1244, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10720069/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10720069</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10720069" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1210/jcem.85.3.6420" target="_blank">Full Text</a>]
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<a id="Donelan2006" class="mim-anchor"></a>
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Donelan, J., Boucher, W., Papadopoulou, N., Lytinas, M., Papaliodis, D., Dobner, P., Theoharides, T. C.
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<strong>Corticotropin-releasing hormone induces skin vascular permeability through a neurotensin-dependent process.</strong>
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Proc. Nat. Acad. Sci. 103: 7759-7764, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16682628/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16682628</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16682628[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16682628" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.0602210103" target="_blank">Full Text</a>]
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<a id="Habib2000" class="mim-anchor"></a>
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Habib, K. E., Weld, K. P., Rice, K. C., Pushkas, J., Champoux, M., Listwak, S., Webster, E. L., Atkinson, A. J., Schulkin, J., Contoreggi, C., Chrousos, G. P., McCann, S. M., Suomi, S. J., Higley, J. D., Gold, P. W.
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<strong>Oral administration of a corticotropin-releasing hormone receptor antagonist significantly attenuates behavioral, neuroendocrine, and autonomic responses to stress in primates.</strong>
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Proc. Nat. Acad. Sci. 97: 6079-6084, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10823952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10823952</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10823952[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10823952" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Inder, W. J., Prickett, T. C. R., Ellis, M. J., Hull, L., Reid, R., Benny, P. S., Livesey, J. H., Donald, R. A.
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<strong>The utility of plasma CRH as a predictor of preterm delivery.</strong>
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J. Clin. Endocr. Metab. 86: 5706-5710, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11739425/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11739425</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11739425" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1210/jcem.86.12.8080" target="_blank">Full Text</a>]
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Zouboulis, C. C., Seltmann, H., Hiroi, N., Chen, W., Young, M., Oeff, M., Scherbaum, W. A., Orfanos, C. E., McCann, S. M., Bornstein, S. R.
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<strong>Corticotropin-releasing hormone: an autocrine hormone that promotes lipogenesis in human sebocytes.</strong>
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Proc. Nat. Acad. Sci. 99: 7148-7153, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12011471/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12011471</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12011471[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12011471" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.102180999" target="_blank">Full Text</a>]
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Cassandra L. Kniffin - updated : 6/17/2015
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Ada Hamosh - updated : 11/1/2012<br>Marla J. F. O'Neill - updated : 5/11/2012<br>Paul J. Converse - updated : 5/3/2012<br>Ada Hamosh - updated : 8/27/2009<br>Paul J. Converse - updated : 6/8/2006<br>Marla J. F. O'Neill - updated : 11/18/2004<br>Victor A. McKusick - updated : 6/14/2002<br>John A. Phillips, III - updated : 6/10/2002<br>John A. Phillips, III - updated : 3/9/2001<br>Victor A. McKusick - updated : 8/4/2000<br>John A. Phillips, III - updated : 4/14/1999<br>Victor A. McKusick - updated : 6/17/1998<br>John A. Phillips, III - updated : 10/27/1997<br>Alan F. Scott - updated : 11/15/1995
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Creation Date:
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Victor A. McKusick : 6/26/1987
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carol : 08/09/2016
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carol : 06/22/2015<br>mcolton : 6/18/2015<br>ckniffin : 6/17/2015<br>alopez : 11/1/2012<br>terry : 11/1/2012<br>terry : 5/11/2012<br>carol : 5/11/2012<br>mgross : 5/4/2012<br>terry : 5/3/2012<br>carol : 9/23/2011<br>alopez : 9/3/2009<br>terry : 8/27/2009<br>mgross : 6/16/2006<br>terry : 6/8/2006<br>tkritzer : 11/18/2004<br>joanna : 3/17/2004<br>cwells : 7/1/2002<br>terry : 6/14/2002<br>alopez : 6/10/2002<br>alopez : 3/9/2001<br>mcapotos : 8/10/2000<br>mcapotos : 8/9/2000<br>terry : 8/4/2000<br>mgross : 4/16/1999<br>mgross : 4/14/1999<br>terry : 6/17/1998<br>joanna : 5/7/1998<br>dholmes : 10/27/1997<br>dholmes : 10/2/1997<br>dholmes : 10/1/1997<br>terry : 4/18/1996<br>terry : 4/12/1996<br>terry : 4/9/1996<br>terry : 3/26/1996<br>mark : 7/24/1995<br>carol : 3/19/1995<br>mimadm : 6/25/1994<br>jason : 6/17/1994<br>carol : 11/2/1993
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<strong>*</strong> 122560
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CORTICOTROPIN-RELEASING HORMONE; CRH
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CORTICOTROPIN-RELEASING FACTOR; CRF
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Cytogenetic location: 8q13.1
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<strong>Cloning and Expression</strong>
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<p>Response to stress in mammals requires an intact hypothalamic-pituitary-adrenal axis. The proximal part of the response is mediated by secretion of corticotropin-releasing hormone (CRH) by the paraventricular nucleus of the hypothalamus. CRH is a 41-amino acid peptide derived by enzymatic cleavage from a 191-amino acid preprohormone. Shibahara et al. (1983) cloned and sequenced the human CRH gene. </p>
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<p>Arbiser et al. (1988) assigned the gene for CRH to 8q13 by somatic cell hybrid and in situ hybridization studies. The absence of secondary hybridization strongly suggested that hypothalamic and placental CRH are transcribed from the same gene. Kellogg et al. (1989) corroborated the assignment to 8q13 by in situ hybridization. Knapp et al. (1993) showed that the homologous gene is located on mouse chromosome 3. </p>
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<p>Sasaki et al. (1987) measured plasma CRH levels during pregnancy, labor, and delivery, and at 1 and 2 hours postpartum in 97 pregnant women. Plasma CRH concentrations progressively increased during pregnancy, correlated well with the weeks of pregnancy, and declined rapidly after delivery. Umbilical cord CRH levels were much lower than those in corresponding maternal plasma, suggesting that CRH is preferentially secreted into the maternal circulation. Maternal plasma CRH-sized material, obtained by affinity chromatography and gel filtration, stimulated ACTH release from anterior pituitary tissue in a dose-dependent manner and was equipotent with rat CRH. Sasaki et al. (1987) suggested that placental CRH might be an important stimulator of the maternal pituitary-adrenal axis during pregnancy, labor, and delivery. </p><p>Campbell et al. (1987) measured plasma CRH levels throughout the third trimester of pregnancy, during labor, and postpartum in 80 normal pregnant women and 49 women with pregnancy-induced hypertension (PIH; see PEE1, 189800). In normal pregnant women, plasma CRH levels increased markedly at 40 weeks and remained so during labor. Women with PIH had plasma CRH levels significantly elevated above that normal range, as did 11 women from the 'normal' group who subsequently went into premature labor. After delivery, plasma CRH returned to normal within 15 hours. Total plasma cortisol levels varied little throughout the third trimester, but increased during labor and remained elevated for 2 to 3 days postpartum. There was, therefore, no correlation between plasma cortisol and CRH, implying that placental CRH is not primarily involved in the control of the maternal hypothalamopituitary adrenal axis during pregnancy. Campbell et al. (1987) also noted that concentrations of CRH in umbilical cord plasma samples were considerably lower than those in the maternal circulation and were close to those in normal nonpregnant adults. </p><p>Robinson et al. (1988) established primary cultures of purified human cytotrophoblasts to examine the effect of glucocorticoids on the expression of the CRH gene in placenta. The authors found that glucocorticoids stimulate synthesis of placental CRH, as demonstrated by slot blot hybridization of RNA prepared from cytotrophoblasts. In addition, using the technique of RNase H digestion of a heteroduplex between CRH mRNA and a synthetic oligonucleotide complementary to the 5-prime CRH mRNA, the authors demonstrated the transcriptional initiation site of the CRH gene. The authors speculated on the role of this regulatory mechanism on the levels of fetal glucocorticoids in the pre- and postparturition periods. </p><p>CRH is made not only in the hypothalamus but also in peripheral tissues, such as T lymphocytes, and is expressed in very large amounts in the human placenta (Robinson et al., 1988). </p><p>McLean et al. (1995) presented evidence that placental secretion of CRH is a marker of the 'placental clock' that is active from an early stage in human pregnancy and determines the length of gestation and the timing of parturition and delivery. Using a prospective, longitudinal cohort study of 485 pregnant women, McLean et al. (1995) demonstrated that placental secretion of CRH, measured as maternal plasma CRH concentration as early as 16 to 20 weeks of gestation, identified groups of women destined to experience normal term, preterm, or post-term delivery. An exponential rise in maternal plasma CRH concentrations with advancing pregnancy is associated with a concomitant fall in concentrations of the specific CRH-binding protein (CRHBP; 122559) in late pregnancy, leading to a rapid increase in circulating levels of bioavailable CRH at the onset of parturition, suggesting that CRH may act directly as a trigger for parturition in humans. </p><p>Behan et al. (1995) observed that the marked reduction in CRF found in Alzheimer disease (AD; e.g., 104300) is due to CRFBP (CRHBP; 122559), a high-affinity binding protein that inactivates CRF. The authors showed that ligands which interfere with this process in AD raise free CRF levels to that of controls. Behan et al. (1995) also studied the learning and memory effects of a CRF-receptor agonist and a CRFBP ligand in rats. </p><p>Asakura et al. (1997) localized immunoreactive corticotropin-releasing factor (IrCRF) and its mRNA to the thecal cells of small antral and mature follicles of the human ovary. A low abundance of IrCRF and mRNA was also detected in stromal cells of both stages of follicles. Greater CRF gene expression was seen in mature than in small antral follicles. CRF receptor (CRFR1; 122561) mRNA signal was found exclusively in thecal cells of mature follicles and moderately in small antral follicles. Granulosa cells were devoid of CRF and CRFR1 mRNAs and proteins. The authors concluded that the thecal compartment of the human ovary contains a CRF system endowed with CRF, CRFR1, and the CRFBP protein while granulosa cells are devoid of this system. </p><p>In choriocarcinoma cell lines, activation of cAMP-dependent pathways increases human CRH reporter gene expression. Scatena and Adler (1998) identified a cAMP-responsive region between -200 and -99 bp of the CRH promoter, distinct from the cAMP response element (CRE) at -220 bp, and also identified a candidate transcription factor present in nuclear extracts of human, but not rodent, choriocarcinoma cell lines. This region, which does not contain a canonical CRE, transfers protein kinase A (EC 2.7.1.37; see 176911) responsiveness to a heterologous promoter. Using electromobility shift assays and methylation and uracil interference studies, Scatena and Adler (1998) localized factor binding to a 20-bp region from -128 to -109 bp of the CRH promoter. This 20-bp fragment exhibited a similar shift in nuclear extracts from both human term placenta and from human JEG-3 cells. Although this factor participates in cAMP-regulated gene expression, competition electrophoretic mobility assays demonstrated that the factor does not bind to a CRE. Furthermore, neither anti-CREB (123810) nor anti-ATF2 (123811) antibodies altered factor binding. The authors concluded that this 58-kD protein is the human-specific CRH activator previously identified (Scatena and Adler, 1996) as contributing to the species-specific expression of CRH in human placenta. </p><p>Xu et al. (2000) investigated the effects of CRH expression in human pituitary corticotroph adenomas (PCAs). CRH mRNA transcripts were demonstrated on paraffin sections using the quantitative in situ hybridization method in 37 of 43 PCAs, including 17 of 22 microadenomas, 15 of 15 macroadenomas, and 5 of 6 locally invasive adenomas according to Hardy's classification of pituitary adenomas. The more important findings were that CRH mRNA signal intensity in pituitary corticotroph adenoma cells was linearly correlated with Ki-67 (176741) tumor growth fractions, and in macroadenoma and locally invasive adenoma cells it was significantly higher than in microadenoma cells. On the other hand, CRH mRNA transcript accumulation was absent or negligible in 10 normal pituitary glands. The authors concluded that CRH from a local source of corticotroph adenoma cells not only has autocrine/paracrine functions in corticotroph adenomatous tissue, but also is an important factor associated with a proliferative potential of PCAs. </p><p>Cheng et al. (2000) explored the effect of cAMP on CRH promoter activity in primary cultures of human placental cells. Both forskolin and 8-bromo-cAMP, activators of protein kinase A, can increase CRH promoter activity 5-fold in transiently transfected human primary placental cells, in a manner that parallels the increase in endogenous CRH peptide. Electrophoretic mobility shift assay and mutation analysis combined with transient transfection demonstrated that in placental cells cAMP stimulates CRH gene expression through a cAMP regulatory element in the proximal CRH promoter region and involves a placental nuclear protein interacting specifically with the cAMP regulatory element. </p><p>It has been suggested that CRH is a placental clock that controls the duration of pregnancy and that the timing of the rise in CRH may permit prediction of the onset of labor. Inder et al. (2001) performed a prospective longitudinal study, in 297 women, to examine the utility of a single second-trimester plasma CRH measurement to predict preterm delivery. Sampling for plasma CRH at 26 weeks' gestation seemed the optimal time point to maximize sensitivity and specificity of the test. The mean (+/- SD) plasma CRH in women at this gestation who eventually delivered after spontaneous labor within 1 week of their due date (39 to 41 weeks, n = 127) was 34.7 +/- 27.0 pM. A plasma CRH of more than 90 pM at 26 weeks' gestation had a sensitivity of 45% and a specificity of 94% for prediction of preterm delivery. The authors concluded that a single measurement of plasma CRH, toward the end of the second trimester, may identify a group at risk for preterm delivery, but over 50% of such deliveries will be unpredicted. These data do not support the routine clinical use of plasma CRH as a predictor of preterm labor. </p><p>Makrigiannakis et al. (2001) observed decreased FASL expression in human extravillous trophoblasts and choriocarcinoma cell lines following treatment with the CRHR1 antagonist antalarmin. In contrast, CRH increased FASL expression and induced apoptosis of activated T cells, and antalarmin inhibited this effect. Treatment of female rats with antalarmin resulted in a marked decrease in implantation sites and live embryos, as well as diminished endometrial Fasl expression. Embryos from T cell-deficient mothers or from syngeneic matings were not rejected when mothers were given antalarmin. Makrigiannakis et al. (2001) proposed that locally produced CRH promotes implantation and the maintenance of early pregnancy by killing activated T cells. </p><p>Sebaceous glands may be involved in a pathway conceptually similar to that of the hypothalamic-pituitary-adrenal (HPA) axis. CRH is the most proximal element of the HPA axis, and it acts as a central coordinator for neuroendocrine and behavioral responses to stress. To examine the probability of an HPA equivalent pathway in sebaceous glands, Zouboulis et al. (2002) investigated the expression of CRH, CRH-binding protein, CRHBP (122559), and CRH receptors (CRHR1, 122561 and CRHR2, 602034) in sebocytes in vitro and their regulation by CRH and several other hormones. CRHR1 was the predominant type, being twice as abundant as CRHR2. CRH was biologically active on human sebocytes; it induced biphasic increase in synthesis of sebaceous lipids, although it did not affect cell viability, cell proliferation, or IL1B (147720)-induced IL8 (146930) release. Zouboulis et al. (2002) interpreted these and other findings as indicating that CRH may be an autocrine hormone for human sebocytes that exerts homeostatic lipogenic activity, whereas testosterone and growth hormone induced CRH negative feedback. The findings implicated CRH in the clinical development of acne, seborrhea, androgenetic alopecia, skin aging, xerosis, and other skin disorders associated with alterations in lipid formation of sebaceous origin. </p><p>Maji et al. (2009) found that peptide and protein hormones, including CRF, in secretory granules of the endocrine system are stored in an amyloid-like cross-beta-sheet-rich conformation, and concluded that functional amyloids in the pituitary and other organs can contribute to normal cell and tissue physiology. </p><p>Lemos et al. (2012) reported that CRF, a neuropeptide released in response to acute stressors and other arousing environmental stimuli, acts in the nucleus accumbens of naive mice to increase dopamine release through coactivation of the receptors CRFR1 and CRFR2. Remarkably, severe-stress exposure completely abolished this effect without recovery for at least 90 days. This loss of CRF's capacity to regulate dopamine release in the nucleus accumbens is accompanied by a switch in the reaction to CRF from appetitive to aversive, indicating a diametric change in the emotional response to acute stressors. Lemos et al. (2012) concluded that their results offer a biologic substrate for the switch in affect which is central to stress-induced depressive disorders. </p>
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<strong>Molecular Genetics</strong>
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<p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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For a discussion of a possible association between autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE; see 600513) and variation in the CRH gene, see 122560.0001.</p>
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<p>To find the importance of CRH in the response of the hypothalamic-pituitary-adrenal axis to stress and its role in fetal development, Muglia et al. (1995) constructed a mouse model of CRH deficiency by targeted mutation in embryonic stem cells. They reported that CRH-deficient mice reveal a fetal glucocorticoid requirement for lung maturation. Postnatally, however, despite marked glucocorticoid deficiency, the mice exhibited normal growth, fertility, and longevity, suggesting that the major role of glucocorticoid occurs during fetal, rather than postnatal, life. </p><p>In adult male rhesus macaques, Habib et al. (2000) evaluated the effects of a lipophilic nonpeptide antagonist to CRH type 1 receptor, antalarmin, on the behavioral, neuroendocrine, and autonomic components of the stress response. After oral administration, significant antalarmin concentrations were detected in the systemic circulation and the cerebrospinal fluid. The monkeys were exposed to an intense social stressor, namely, placement of 2 unfamiliar males in adjacent cages separated only by a transparent Plexiglas screen. Antalarmin significantly inhibited a repertoire of behaviors associated with anxiety and fear, such as body tremors, grimacing, teeth gnashing, urination, and defecation. In contrast, antalarmin increased exploratory and sexual behaviors that are normally suppressed during stress. Moreover, antalarmin significantly diminished the increases in cerebrospinal fluid CRH as well as the pituitary-adrenal, sympathetic, and adrenal medullary responses to stress. Habib et al. (2000) suggested that a CRH type 1 receptor antagonist may be of therapeutic value in human psychiatric, reproductive, and cardiovascular disorders associated with CRH system hyperactivity. </p><p>Using a turpentine-induced model of subacute inflammation in Crh -/- mice, Venihaki et al. (2001) demonstrated that during inflammation Crh is required for a normal adrenocorticotropin hormone (ACTH) increase but not for adrenal corticosterone rise. A paradoxical increase of plasma interleukin-6 (IL6; 147620) associated with Crh deficiency suggested that regulation of Il6 release during inflammation is Crh dependent. Venihaki et al. (2001) also demonstrated that adrenal Il6 expression is Crh dependent, as its basal and inflammation-induced expression was blocked by Crh deficiency. Mice deficient in both Crh and Il6 had a flat hypothalamic-pituitary-adrenal response to inflammation. </p><p>Donelan et al. (2006) used intradermal injection of various peptides to assess vascular permeability, as measured by Evans blue extravasation, in rat skin. They found that Crh and neurotensin (NTS; 162650) potently induced vascular permeability. The effect of Crh and Nts was blocked by a neurotensin receptor (see NTSR1; 162651) antagonist and did not occur in Nts -/- mice. RT-PCR analysis showed that Crh and Nts were present in dorsal root ganglia and that Crhr was expressed on mouse skin mast cells. Donelan et al. (2006) concluded that NTS is involved in the action of CRH. They suggested that mast cell-neuron interactions and mast cell activation may be involved in the pathophysiology of skin conditions such as atopic dermatitis, urticaria, and psoriasis. </p>
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<h4>
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<span class="mim-font">
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<strong>History</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>In a consanguineous kindred in Israel, Mandel et al. (1990) identified 11 children with autosomal recessive hypothalamic corticotropin deficiency. Death without diagnosis occurred in 7. Four of the affected children were studied extensively; 2 were diagnosed prenatally. The first diagnosed patient presented at age 2 months with hypoglycemia, hepatitis, facial dysmorphism, convulsions, and agenesis of the corpus callosum. The prenatal diagnosis was suggested by low maternal urinary estriol and confirmed at birth by undetectable levels of cortisol and ACTH (176830). Treatment with cortisol resulted in normal development. Growth hormone deficiency and a thyroid organification defect were secondary to adrenal insufficiency. The disorder was clearly an autosomal recessive. Majzoub (1995) stated that the findings in this Bedouin family had not been reported in full. Linkage was being used to determine whether CRH deficiency was indeed present.</p>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>1 Selected Example):</strong>
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</span>
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</h4>
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<div>
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<p />
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 VARIANT OF UNKNOWN SIGNIFICANCE</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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CRH, PRO30ARG
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<br />
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SNP: rs748404250,
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gnomAD: rs748404250,
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ClinVar: RCV000172993, RCV000192059, RCV004019949
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<span class="mim-text-font">
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<p>This variant is classified as a variant of unknown significance because its contribution to autosomal dominant nocturnal frontal lobe epilepsy (see ENFL1, 600513) has not been confirmed.</p><p>In 2 Italian sibs with autosomal dominant nocturnal frontal lobe epilepsy, Sansoni et al. (2013) identified a heterozygous c.89C-G transversion (c.89C-G, NM_000756.2) in exon 2 of the CRH gene, resulting in a pro30-to-arg (P30R) substitution at a highly conserved residue in the pro-sequence of the protein. The variant was not found in 100 ancestry-matched controls or in public databases. In vitro functional expression studies in neural cells showed that the variant resulted in a lower level of the CRH precursor protein within the cell and slower excretion of the mature hormone. The variant protein showed higher colocalization in the Golgi apparatus compared to wildtype. The findings suggested that the variant resulted in a delay in posttranslational protein processing, leading to degradation and/or slower release of the mature peptide. The released mature protein encoded by the variant was identical to the wildtype protein, since the variant is cleaved from the precursor intracellullarly. Sansoni et al. (2013) postulated that the mutation impairs prompt release of the hormone and alters immediate response to stress agents. The patients had onset of nocturnal motor episodes at ages 10 and 11 years, respectively. The episodes occurred almost nightly at first, and were characterized by sudden elevation of the head and trunk, often associated with manual and pedal motor activity. Frequency of episodes in 1 patient decreased in her late twenties. The deceased father reportedly had REM sleep behavior disorder, but his DNA was not available. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>See Also:</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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Kyllo et al. (1996)
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Arbiser, J. L., Morton, C. C., Bruns, G. A. P., Majzoub, J. A.
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<strong>Human corticotropin releasing hormone gene is located on the long arm of chromosome 8.</strong>
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Cytogenet. Cell Genet. 47: 113-116, 1988.
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[PubMed: 3259914]
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[Full Text: https://doi.org/10.1159/000132525]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Asakura, H., Zwain, I. H., Yen, S. S. C.
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<strong>Expression of genes encoding corticotropin-releasing factor (CRF), type 1 CRF receptor, and CRF-binding protein and localization of the gene products in the human ovary.</strong>
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J. Clin. Endocr. Metab. 82: 2720-2725, 1997.
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[PubMed: 9253360]
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[Full Text: https://doi.org/10.1210/jcem.82.8.4119]
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<li>
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<p class="mim-text-font">
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Behan, D. P., Heinrichs, S. C., Troncoso, J. C., Liu, X.-J., Kawas, C. H., Ling, N., De Souza, E. B.
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<strong>Displacement of corticotropin releasing factor from its binding protein as a possible treatment for Alzheimer's disease.</strong>
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Nature 378: 284-287, 1995.
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[PubMed: 7477348]
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</li>
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<li>
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<p class="mim-text-font">
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Campbell, E. A., Linton, E. A., Wolfe, C. D. A., Scraggs, P. R., Jones, M. T., Lowry, P. J.
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<strong>Plasma corticotropin-releasing hormone concentrations during pregnancy and parturition.</strong>
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J. Clin. Endocr. Metab. 64: 1054-1059, 1987.
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[PubMed: 3494036]
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[Full Text: https://doi.org/10.1210/jcem-64-5-1054]
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</p>
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<li>
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<p class="mim-text-font">
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Cheng, Y.-H., Nicholson, R. C., King, B., Chan, E.-C., Fitter, J. T., Smith, R.
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<strong>Corticotropin-releasing hormone gene expression in primary placental cells is modulated by cyclic adenosine 3-prime,5-prime-monophosphate.</strong>
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J. Clin. Endocr. Metab. 85: 1239-1244, 2000.
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[PubMed: 10720069]
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[Full Text: https://doi.org/10.1210/jcem.85.3.6420]
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<li>
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<p class="mim-text-font">
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Donelan, J., Boucher, W., Papadopoulou, N., Lytinas, M., Papaliodis, D., Dobner, P., Theoharides, T. C.
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<strong>Corticotropin-releasing hormone induces skin vascular permeability through a neurotensin-dependent process.</strong>
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Proc. Nat. Acad. Sci. 103: 7759-7764, 2006.
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[PubMed: 16682628]
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[Full Text: https://doi.org/10.1073/pnas.0602210103]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Habib, K. E., Weld, K. P., Rice, K. C., Pushkas, J., Champoux, M., Listwak, S., Webster, E. L., Atkinson, A. J., Schulkin, J., Contoreggi, C., Chrousos, G. P., McCann, S. M., Suomi, S. J., Higley, J. D., Gold, P. W.
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<strong>Oral administration of a corticotropin-releasing hormone receptor antagonist significantly attenuates behavioral, neuroendocrine, and autonomic responses to stress in primates.</strong>
|
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Proc. Nat. Acad. Sci. 97: 6079-6084, 2000.
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[PubMed: 10823952]
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[Full Text: https://doi.org/10.1073/pnas.97.11.6079]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Inder, W. J., Prickett, T. C. R., Ellis, M. J., Hull, L., Reid, R., Benny, P. S., Livesey, J. H., Donald, R. A.
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<strong>The utility of plasma CRH as a predictor of preterm delivery.</strong>
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J. Clin. Endocr. Metab. 86: 5706-5710, 2001.
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[PubMed: 11739425]
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[Full Text: https://doi.org/10.1210/jcem.86.12.8080]
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<li>
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<p class="mim-text-font">
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Kellogg, J., Luty, J. A., Thompson, R., Luo, X. Y., Magenis, R. E., Litt, M.
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<strong>Corticotropin releasing hormone (CRH) maps to human chromosome 8 and identifies a TaqI RFLP.</strong>
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Cytogenet. Cell Genet. 51: 1022, 1989.
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</p>
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<p class="mim-text-font">
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Knapp, L. T., Keegan, C. E., Seasholtz, A. F., Camper, S. A.
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<strong>Corticotropin-releasing hormone (Crh) maps to mouse chromosome 3.</strong>
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Mammalian Genome 4: 615-617, 1993.
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[PubMed: 8268662]
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[Full Text: https://doi.org/10.1007/BF00361396]
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<p class="mim-text-font">
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Kyllo, J. H., Collins, M. M., Vetter, K. L., Cuttler, L., Rosenfield, R. L., Donohoue, P. A.
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<strong>Linkage of congenital isolated adrenocorticotropic hormone deficiency to the corticotropin releasing hormone locus using simple sequence repeat polymorphisms.</strong>
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Am. J. Med. Genet. 62: 262-267, 1996.
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[PubMed: 8882784]
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[Full Text: https://doi.org/10.1002/(SICI)1096-8628(19960329)62:3<262::AID-AJMG11>3.0.CO;2-I]
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Lemos, J. C., Wanat, M. J., Smith, J. S., Reyes, B. A. S., Hollon, N. G., Van Bockstaele, E. J., Chavkin, C., Phillips, P. E. M.
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<strong>Severe stress switches CRF action in the nucleus accumbens from appetitive to aversive.</strong>
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Nature 490: 402-406, 2012.
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[PubMed: 22992525]
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Maji, S. K., Perrin, M. H., Sawaya, M. R., Jessberger, S., Vadodaria, K., Rissman, R. A., Singru, P. S., Nilsson, K. P. R., Simon, R., Schubert, D., Eisenberg, D., Rivier, J., Sawchenko, P., Vale, W., Riek, R.
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<strong>Functional amyloids as natural storage of peptide hormones in pituitary secretory granules.</strong>
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Makrigiannakis, A., Zoumakis, E., Kalantaridou, S., Coutifaris, C., Margioris, A. N., Coukos, G., Rice, K. C., Gravanis, A., Chrousos, G. P.
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<strong>Corticotropin-releasing hormone promotes blastocyst implantation and early maternal tolerance.</strong>
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Mandel, H., Berant, M., Gotfried, E., Hochberg, Z.
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<strong>Autosomal recessive hypothalamic corticotropin deficiency: a new entity and its metabolic consequences. (Abstract)</strong>
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McLean, M., Bisits, A., Davies, J., Woods, R., Lowry, P., Smith, R.
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<strong>A placental clock controlling the length of human pregnancy.</strong>
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<p class="mim-text-font">
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Muglia, L., Jacobson, L., Dikkes, P., Majzoub, J. A.
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<strong>Corticotropin-releasing hormone deficiency reveals major fetal but not adult glucocorticoid need.</strong>
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Nature 373: 427-432, 1995.
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[PubMed: 7830793]
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Robinson, B. G., Emanuel, R. L., Frim, D. M., Majzoub, J. A.
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<strong>Glucocorticoid stimulates expression of corticotropin-releasing hormone gene in human placenta.</strong>
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[PubMed: 2839838]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Sansoni, V., Forcella, M., Mozzi, A., Fusi, P., Ambrosini, R., Ferini-Strambi, L., Combi, R.
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<strong>Functional characterization of a CRH missense mutation identified in an ADNFLE family.</strong>
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PLoS One 8: e61306, 2013. Note: Electronic Article.
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[PubMed: 23593457]
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[Full Text: https://doi.org/10.1371/journal.pone.0061306]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Sasaki, A., Shinkawa, O., Margioris, A. N., Liotta, A. S., Sato, S., Murakami, O., Go, M., Shimizu, Y., Hanew, K., Yoshinaga, K.
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<strong>Immunoreactive corticotropin-releasing hormone in human plasma during pregnancy, labor, and delivery.</strong>
|
|
J. Clin. Endocr. Metab. 64: 224-229, 1987.
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[PubMed: 3491832]
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[Full Text: https://doi.org/10.1210/jcem-64-2-224]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Scatena, C. D., Adler, S.
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<strong>Trans-acting factors dictate the species-specific placental expression of corticotropin-releasing factor genes in choriocarcinoma cell lines.</strong>
|
|
Endocrinology 137: 3000-3008, 1996.
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[PubMed: 8770924]
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[Full Text: https://doi.org/10.1210/endo.137.7.8770924]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Scatena, C. D., Adler, S.
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<strong>Characterization of a human-specific regulator of placental corticotropin-releasing hormone.</strong>
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Molec. Endocr. 12: 1228-1240, 1998.
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[PubMed: 9717848]
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[Full Text: https://doi.org/10.1210/mend.12.8.0150]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Shibahara, S., Morimoto, Y., Furutani, Y., Notake, M., Takahashi, H., Shimizu, S., Horikawa, S., Numa, S.
|
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<strong>Isolation and sequence analysis of the human corticotropin-releasing factor precursor gene.</strong>
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EMBO J. 2: 775-779, 1983.
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[Full Text: https://doi.org/10.1002/j.1460-2075.1983.tb01499.x]
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Venihaki, M., Dikkes, P., Carrigan, A., Karalis, K. P.
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<strong>Corticotropin-releasing hormone regulates IL-6 expression during inflammation.</strong>
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J. Clin. Invest. 108: 1159-1166, 2001.
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[PubMed: 11602623]
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[Full Text: https://doi.org/10.1172/JCI12869]
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Xu, B., Sano, T., Yamada, S., Li, C. C., Hirokawa, M.
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<strong>Expression of corticotropin-releasing hormone messenger ribonucleic acid in human pituitary corticotroph adenomas associated with proliferative potential.</strong>
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J. Clin. Endocr. Metab. 85: 1220-1225, 2000.
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[Full Text: https://doi.org/10.1210/jcem.85.3.6471]
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Zouboulis, C. C., Seltmann, H., Hiroi, N., Chen, W., Young, M., Oeff, M., Scherbaum, W. A., Orfanos, C. E., McCann, S. M., Bornstein, S. R.
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<strong>Corticotropin-releasing hormone: an autocrine hormone that promotes lipogenesis in human sebocytes.</strong>
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Proc. Nat. Acad. Sci. 99: 7148-7153, 2002.
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[PubMed: 12011471]
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[Full Text: https://doi.org/10.1073/pnas.102180999]
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Cassandra L. Kniffin - updated : 6/17/2015<br>Ada Hamosh - updated : 11/1/2012<br>Marla J. F. O'Neill - updated : 5/11/2012<br>Paul J. Converse - updated : 5/3/2012<br>Ada Hamosh - updated : 8/27/2009<br>Paul J. Converse - updated : 6/8/2006<br>Marla J. F. O'Neill - updated : 11/18/2004<br>Victor A. McKusick - updated : 6/14/2002<br>John A. Phillips, III - updated : 6/10/2002<br>John A. Phillips, III - updated : 3/9/2001<br>Victor A. McKusick - updated : 8/4/2000<br>John A. Phillips, III - updated : 4/14/1999<br>Victor A. McKusick - updated : 6/17/1998<br>John A. Phillips, III - updated : 10/27/1997<br>Alan F. Scott - updated : 11/15/1995
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Victor A. McKusick : 6/26/1987
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