Corticotropin-releasing hormone

Corticotropin releasing hormone
PDB rendering based on 1go9.
Identifiers
Symbols	CRH ; CRF
External IDs	Template:OMIM5 Template:MGI HomoloGene: 599
Gene ontology Molecular function Template:GNF GO Cellular component Template:GNF GO Template:GNF GO Biological process Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO
RNA expression pattern
More reference expression data
Orthologs
Template:GNF Ortholog box
Species	Human	Mouse
Entrez	n/a	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
Location (UCSC)	n/a	n/a
PubMed search	n/a	n/a

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Corticotropin-releasing hormone (CRH), originally named corticotropin-releasing factor (CRF), and also called corticoliberin, is a polypeptide hormone and neurotransmitter involved in the stress response.

Corticotropin-releasing hormone (CRH) is a 41-amino acid peptide derived from a 191-amino acid preprohormone. CRH is secreted by the paraventricular nucleus (PVN) of the hypothalamus in response to stress. Marked reduction in CRH has been observed in association with Alzheimer disease, and autosomal recessive hypothalamic corticotropin deficiency has multiple and potentially-fatal metabolic consequences including hypoglycemia and hepatitis. In addition to being produced in the hypothalamus, CRH is also synthesized in peripheral tissues, such as T lymphocytes, and is highly expressed in the placenta. In the placenta, CRH is a marker that determines the length of gestation and the timing of parturition and delivery. A rapid increase in circulating levels of CRH occurs at the onset of parturition, suggesting that, in addition to its metabolic functions, CRH may act as a trigger for parturition.

Hormonal actions

CRH is produced by neuroendocrine cells in the paraventricular nucleus of the hypothalamus and is released from neurosecretory terminals of these neurons into the primary capillary plexus of the hypothalamo-hypophyseal portal system. The portal system carries the CRH to the anterior lobe of the pituitary, where it stimulates corticotropes to secrete corticotropin (ACTH) and other biologically-active substances (for example β-endorphin).

ά-helical CRH-(9--41) acts as a CRH antagonist.

Psychopharmacy

The CRH-1 receptor antagonist pexacerfont is currently under investigation for the treatment of Generalized Anxiety Disorder in women. Another CRH-1 antagonist antalarmin has been researched in animal studies for the treatment of anxiety, depression and other conditions, but no human trials with this compound have been carried out.

Also, abnormal levels of CRH have been found in the cerebrospinal fluid of suicide victims.

Role in parturition

CRH is also synthesized by the placenta and seems to determine the duration of pregnancy.

Levels rise towards birth and current theory suggests three roles of CRH in parturition.
1. Increases level so dehydroepiandrosterone (DHAS) directly by action on the fetal adrenal gland, and indirectly via the mother's pituitary gland. DHAS has a role in preparing for and stimulating cervical contractions.
2. Increases prostaglandin availability in uteroplacental tissues. Prostaglandins activate cervical contractions.
3. Prior to parturition it may have a role inhibiting contractions, through increasing cAMP levels in the myometrium.

In culture, trophoblast CRH is inhibited by progesterone, which remains high throughout pregnancy. It's release is stimultated by glucocorticoids and catecholamines, which increase prior to parturition lifting this progesterone block.

Structure

The 41-amino acid sequence of CRH was first discovered in sheep by Vale et al in 1981. Its full sequence is

SQEPPISLDLTFHLLREVLEMTKADQLAQQAHSNRKLLDIA

See also

• Corticotropin-releasing hormone receptor
• Proopiomelanocortin
• Hypothalamic-pituitary-adrenal axis

Further reading

• Florio P, Severi FM, Ciarmela P; et al. (2003). "Placental stress factors and maternal-fetal adaptive response: the corticotropin-releasing factor family". Endocrine. 19 (1): 91–102. PMID 12583606.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Florio P, Rossi M, Sigurdardottir M; et al. (2004). "Paracrine regulation of endometrial function: interaction between progesterone and corticotropin-releasing factor (CRF) and activin A.". Steroids. 68 (10–13): 801–7. PMID 14667971.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Vamvakopoulos NC, Karl M, Mayol V; et al. (1990). "Structural analysis of the regulatory region of the human corticotropin releasing hormone gene". FEBS Lett. 267 (1): 1–5. doi:10.1016/0014-5793(90)80272-K. PMID 2365075.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Robinson BG, D'Angio LA, Pasieka KB, Majzoub JA (1989). "Preprocorticotropin releasing hormone: cDNA sequence and in vitro processing". Mol. Cell. Endocrinol. 61 (2): 175–80. doi:10.1016/0303-7207(89)90128-7. PMID 2783917.CS1 maint: Multiple names: authors list (link)
• Arbiser JL, Morton CC, Bruns GA, Majzoub JA (1988). "Human corticotropin releasing hormone gene is located on the long arm of chromosome 8". Cytogenet. Cell Genet. 47 (3): 113–6. PMID 3259914.CS1 maint: Multiple names: authors list (link)
• Sasaki A, Tempst P, Liotta AS; et al. (1988). "Isolation and characterization of a corticotropin-releasing hormone-like peptide from human placenta". J. Clin. Endocrinol. Metab. 67 (4): 768–73. PMID 3262120.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Shibahara S, Morimoto Y, Furutani Y; et al. (1984). "Isolation and sequence analysis of the human corticotropin-releasing factor precursor gene". EMBO J. 2 (5): 775–9. PMID 6605851.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Behan DP, Heinrichs SC, Troncoso JC; et al. (1995). "Displacement of corticotropin releasing factor from its binding protein as a possible treatment for Alzheimer's disease". Nature. 378 (6554): 284–7. doi:10.1038/378284a0. PMID 7477348.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Kawahito Y, Sano H, Mukai S; et al. (1996). "Corticotropin releasing hormone in colonic mucosa in patients with ulcerative colitis". Gut. 37 (4): 544–51. PMID 7489943.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• McLean M, Bisits A, Davies J; et al. (1995). "A placental clock controlling the length of human pregnancy". Nat. Med. 1 (5): 460–3. doi:10.1038/nm0595-460. PMID 7585095.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Slominski A, Ermak G, Hwang J; et al. (1995). "Proopiomelanocortin, corticotropin releasing hormone and corticotropin releasing hormone receptor genes are expressed in human skin". FEBS Lett. 374 (1): 113–6. doi:10.1016/0014-5793(95)01090-2. PMID 7589495.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Sutton SW, Behan DP, Lahrichi SL; et al. (1995). "Ligand requirements of the human corticotropin-releasing factor-binding protein". Endocrinology. 136 (3): 1097–102. doi:10.1210/en.136.3.1097. PMID 7867564.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Vamvakopoulos NC, Chrousos GP (1994). "Structural organization of the 5' flanking region of the human corticotropin releasing hormone gene". DNA Seq. 4 (3): 197–206. PMID 8161822.
• Perrin MH, Donaldson CJ, Chen R; et al. (1994). "Cloning and functional expression of a rat brain corticotropin releasing factor (CRF) receptor". Endocrinology. 133 (6): 3058–61. PMID 8243338.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Romier C, Bernassau JM, Cambillau C, Darbon H (1993). "Solution structure of human corticotropin releasing factor by 1H NMR and distance geometry with restrained molecular dynamics". Protein Eng. 6 (2): 149–56. PMID 8386360.CS1 maint: Multiple names: authors list (link)
• Liaw CW, Grigoriadis DE, Lovenberg TW; et al. (1997). "Localization of ligand-binding domains of human corticotropin-releasing factor receptor: a chimeric receptor approach". Mol. Endocrinol. 11 (7): 980–5. PMID 9178757.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Timpl P, Spanagel R, Sillaber I; et al. (1998). "Impaired stress response and reduced anxiety in mice lacking a functional corticotropin-releasing hormone receptor 1". Nat. Genet. 19 (2): 162–6. doi:10.1038/520. PMID 9620773.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Perone MJ, Murray CA, Brown OA; et al. (1998). "Procorticotrophin-releasing hormone: endoproteolytic processing and differential release of its derived peptides within AtT20 cells". Mol. Cell. Endocrinol. 142 (1–2): 191–202. doi:10.1016/S0303-7207(98)00104-X. PMID 9783915.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Willenberg HS, Bornstein SR, Hiroi N; et al. (2000). "Effects of a novel corticotropin-releasing-hormone receptor type I antagonist on human adrenal function". Mol. Psychiatry. 5 (2): 137–41. doi:10.1038/sj.mp.4000720. PMID 10822340.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Saeed B, Fawcett M, Self C (2001). "Corticotropin-releasing hormone binding to the syncytiotrophoblast membranes". Eur. J. Clin. Invest. 31 (2): 125–30. doi:10.1046/j.1365-2362.2001.00770.x. PMID 11168450.CS1 maint: Multiple names: authors list (link)