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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's 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.[1]

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).

α-helical CRH-(9–41) acts as a CRH antagonist.[2]

Psychopharmacy[]

The CRH-1 receptor antagonist pexacerfont is currently under investigation for the treatment of Generalized anxiety disorder in women.[3] 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.[4]

Recent research has linked the activation of the CRH1 receptor with the euphoric feelings that accompany alcohol consumption. A CRH1 receptor antagonist developed by Pfizer, CP-154,526 is under investigation for the potential treatment of alcoholism.[5][6]

Role in parturition[]

CRH is also synthesized by the placenta and seems to determine the duration of pregnancy.[7]

Levels rise towards birth and current theory suggests three roles of CRH in parturition:[8]

  • Increases level so dehydroepiandrosterone (DHEA) directly by action on the fetal adrenal gland, and indirectly via the mother's pituitary gland. DHEA has a role in preparing for and stimulating cervical contractions.
  • Increases prostaglandin availability in uteroplacental tissues. Prostaglandins activate cervical contractions.
  • 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. Its release is stimultated by glucocorticoids and catecholamines, which increase prior to parturition lifting this progesterone block.[9]

Structure[]

The 41-amino acid sequence of CRH was first discovered in sheep by Vale et al in 1981.[10] Its full sequence is:

  • SQEPPISLDLTFHLLREVLEMTKADQLAQQAHSNRKLLDIA

See also[]

References[]

  1. Entrez Gene: CRH corticotropin releasing hormone.
  2. Santos J, Saunders PR, Hanssen NP, Yang PC, Yates D, Groot JA, Perdue MH (August 1999). Corticotropin-releasing hormone mimics stress-induced colonic epithelial pathophysiology in the rat. Am. J. Physiol. 277 (2 Pt 1): G391–9.
  3. Study of Pexacerfont (BMS-562086) in the Treatment of Outpatients With Generalized Anxiety Disorder. ClinicalTrials.gov. URL accessed on 2008-08-03.
  4. Arató M, Bánki CM, Bissette G, Nemeroff CB (1989). Elevated CSF CRF in suicide victims. Biol. Psychiatry 25 (3): 355–9.
  5. Drug Has Potential To Prevent Alcoholics From Relapsing. Science News. ScienceDaily. URL accessed on 2008-08-09.
  6. Pastor R, McKinnon CS, Scibelli AC, Burkhart-Kasch S, Reed C, Ryabinin AE, Coste SC, Stenzel-Poore MP, Phillips TJ (July 2008). Corticotropin-releasing factor-1 receptor involvement in behavioral neuroadaptation to ethanol: a urocortin1-independent mechanism. Proc. Natl. Acad. Sci. U.S.A. 105 (26): 9070–5.
  7. Kimball JW. Hormones of the Hypothalamus. Kimball's Biology Pages. URL accessed on 2008-08-03.
  8. Lye S, Challis JRG (2001). "Chapter 12: Parturition" Bocking AD, Harding R Fetal growth and development, pages 241-266, Cambridge, UK: Cambridge University Press.
  9. Jones SA, Brooks AN, Challis JR (April 1989). Steroids modulate corticotropin-releasing hormone production in human fetal membranes and placenta. J. Clin. Endocrinol. Metab. 68 (4): 825–30.
  10. Vale W, Spiess J, Rivier C, Rivier J (September 1981). Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin. Science (journal) 213 (4514): 1394–7.

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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • McLean M, Bisits A, Davies J, et al. (1995). A placental clock controlling the length of human pregnancy.. Nat. Med. 1 (5): 460-3.
  • 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.
  • Sutton SW, Behan DP, Lahrichi SL, et al. (1995). Ligand requirements of the human corticotropin-releasing factor-binding protein.. Endocrinology 136 (3): 1097-102.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Saeed B, Fawcett M, Self C (2001). Corticotropin-releasing hormone binding to the syncytiotrophoblast membranes.. Eur. J. Clin. Invest. 31 (2): 125-30.




Further references[]

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  • Aird, F., Halasz, I., & Redei, E. (1997). Ontogeny of hypothalamic corticotropin-releasing factor and anterior pituitary pro-opiomelanocortin expression in male and female offspring of alcohol-exposed and adrenalectomized dams: Alcoholism: Clinical and Experimental Research Vol 21(9) Dec 1997, 1560-1566.
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Target-derived NGF, BDNF, NT-3

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