Corticotropin-releasing hormone
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| Location (UCSC) | Chr 8: 66.18 – 66.18 Mb | Chr 3: 19.75 – 19.75 Mb | |||||||
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Corticotropin-releasing hormone (CRH) (also known as corticotropin-releasing factor (CRF) or corticoliberin; corticotropin may also be spelled corticotrophin) is a
Corticotropin-releasing hormone (CRH) is a 41-amino acid peptide derived from a 196-amino acid preprohormone. CRH is secreted by the
In addition to being produced in the hypothalamus, CRH is also synthesized in peripheral tissues, such as
A
Actions and psychopharmacology
CRH is produced in response to stress, predominantly by
In the short term, CRH can suppress appetite, increase subjective feelings of anxiety, and perform other functions like boosting attention.[8]
During chronic stress conditions such as post-traumatic stress disorder (PTSD), blood serum levels of CRH are decreased in combat veterans with PTSD compared to healthy individuals.[9] It is believed that chronic stress enhances the negative feedback inhibition of the HPA axis, resulting in lower CRH levels and HPA function.[10][11][12]
Abnormally high levels of CRH have been found in people with
Corticotropin-releasing hormone has been shown to
The CRH-1 receptor antagonist pexacerfont is currently under investigation for the treatment of generalized anxiety disorder.[21] Another CRH-1 antagonist antalarmin has been researched[citation needed] in animal studies for the treatment of anxiety, depression and other conditions, but no human trials with this compound have been carried out.
The activation of the CRH1 receptor has been linked 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.[22][23]
Increased CRH production has been observed to be associated with Alzheimer's disease.[6]
Although one action of CRH is immunosuppression via the action of cortisol, CRH itself can actually heighten the immune system's inflammation response, a process being investigated in multiple sclerosis research.[24]
Autosomal recessive hypothalamic corticotropin deficiency has multiple and potentially fatal metabolic consequences including hypoglycemia.[5]
Alpha-helical CRH-(9–41) acts as a CRH antagonist.[25]
Role in parturition
CRH is synthesized by the placenta and seems to determine the duration of pregnancy.[26]
Levels rise towards the end of pregnancy just before birth and current theory suggests three roles of CRH in parturition:[27]
- Increases levels of 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 stimulated by
Structure
The 41-amino acid sequence of CRH was first discovered in sheep by Vale et al. in 1981.[29] Its full sequence is:
- SQEPPISLDLTFHLLREVLEMTKADQLAQQAHSNRKLLDIA
The rat and human peptides are identical and differ from the ovine sequence only by 7 amino acids.[30]
- SEEPPISLDLTFHLLREVLEMARAEQLAQQAHSNRKLMEII
Role in non-mammalian vertebrates
In mammals, studies suggest that CRH has no significant
See also
- Corticotropin-releasing hormone receptor
- ACTH
- Glucocorticoids
- Proopiomelanocortin
- Hypothalamic-pituitary-adrenal axis
- Cushing's syndrome
- Addison's disease
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000147571 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000049796 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b c d "Entrez Gene: CRH corticotropin releasing hormone".
- ^ PMID 7653697.
- ^ "Corticotrophin-releasing hormone". 5 September 2012. Society for Endocrinology. Archived from the original on 20 October 2016. Retrieved 9 July 2013.
- PMID 31467945.
- PMID 35211666.
- S2CID 1510508.
- PMID 24456850.
- PMID 29264511.
- S2CID 23478346.
- S2CID 19665375.
- PMID 10598591.
- S2CID 6235036.
- S2CID 5017743.
- PMID 14744257.
- PMID 18478589.
- PMID 31055007.
- ^ "Study of Pexacerfont (BMS-562086) in the Treatment of Outpatients With Generalized Anxiety Disorder". ClinicalTrials.gov. 1 August 2008. Retrieved 3 August 2008.
- ^ "Drug Has Potential To Prevent Alcoholics From Relapsing". Science News. ScienceDaily. 2 August 2008. Retrieved 9 August 2008.
- PMID 18591672.
- PMID 8211095.
- S2CID 4457633.
- PMID 4145789. Archived from the originalon 27 June 2012. Retrieved 3 August 2008.
- ISBN 978-0-521-64543-0.
- PMID 2537843.
- PMID 6267699.
- PMID 2982307.
- PMID 12379493.
- PMID 16337947.
Further reading
- Florio P, Severi FM, Ciarmela P, Fiore G, Calonaci G, Merola A, et al. (October 2002). "Placental stress factors and maternal-fetal adaptive response: the corticotropin-releasing factor family". Endocrine. 19 (1): 91–102. S2CID 39099605.
- Florio P, Rossi M, Sigurdardottir M, Ciarmela P, Luisi S, Viganò P, et al. (November 2003). "Paracrine regulation of endometrial function: interaction between progesterone and corticotropin-releasing factor (CRF) and activin A". Steroids. 68 (10–13): 801–807. S2CID 20953018.
- Vamvakopoulos NC, Karl M, Mayol V, Gomez T, Stratakis CA, Margioris A, et al. (July 1990). "Structural analysis of the regulatory region of the human corticotropin releasing hormone gene". FEBS Letters. 267 (1): 1–5. S2CID 27597930.
- Robinson BG, D'Angio LA, Pasieka KB, Majzoub JA (February 1989). "Preprocorticotropin releasing hormone: cDNA sequence and in vitro processing". Molecular and Cellular Endocrinology. 61 (2): 175–180. S2CID 31350703.
- Arbiser JL, Morton CC, Bruns GA, Majzoub JA (1988). "Human corticotropin releasing hormone gene is located on the long arm of chromosome 8". Cytogenetics and Cell Genetics. 47 (3): 113–116. PMID 3259914.
- Sasaki A, Tempst P, Liotta AS, Margioris AN, Hood LE, Kent SB, et al. (October 1988). "Isolation and characterization of a corticotropin-releasing hormone-like peptide from human placenta". The Journal of Clinical Endocrinology and Metabolism. 67 (4): 768–773. PMID 3262120.
- Shibahara S, Morimoto Y, Furutani Y, Notake M, Takahashi H, Shimizu S, et al. (1984). "Isolation and sequence analysis of the human corticotropin-releasing factor precursor gene". The EMBO Journal. 2 (5): 775–779. PMID 6605851.
- Behan DP, Heinrichs SC, Troncoso JC, Liu XJ, Kawas CH, Ling N, et al. (November 1995). "Displacement of corticotropin releasing factor from its binding protein as a possible treatment for Alzheimer's disease". Nature. 378 (6554): 284–287. S2CID 4305815.
- Kawahito Y, Sano H, Mukai S, Asai K, Kimura S, Yamamura Y, et al. (October 1995). "Corticotropin releasing hormone in colonic mucosa in patients with ulcerative colitis". Gut. 37 (4): 544–551. PMID 7489943.
- McLean M, Bisits A, Davies J, Woods R, Lowry P, Smith R (May 1995). "A placental clock controlling the length of human pregnancy". Nature Medicine. 1 (5): 460–463. S2CID 27897688.
- Slominski A, Ermak G, Hwang J, Chakraborty A, Mazurkiewicz JE, Mihm M (October 1995). "Proopiomelanocortin, corticotropin releasing hormone and corticotropin releasing hormone receptor genes are expressed in human skin". FEBS Letters. 374 (1): 113–116. S2CID 37397132.
- Sutton SW, Behan DP, Lahrichi SL, Kaiser R, Corrigan A, Lowry P, et al. (March 1995). "Ligand requirements of the human corticotropin-releasing factor-binding protein". Endocrinology. 136 (3): 1097–1102. PMID 7867564.
- Vamvakopoulos NC, Chrousos GP (1994). "Structural organization of the 5' flanking region of the human corticotropin releasing hormone gene". DNA Sequence. 4 (3): 197–206. PMID 8161822.
- Perrin MH, Donaldson CJ, Chen R, Lewis KA, Vale WW (December 1993). "Cloning and functional expression of a rat brain corticotropin releasing factor (CRF) receptor". Endocrinology. 133 (6): 3058–3061. PMID 8243338.
- Romier C, Bernassau JM, Cambillau C, Darbon H (February 1993). "Solution structure of human corticotropin releasing factor by 1H NMR and distance geometry with restrained molecular dynamics". Protein Engineering. 6 (2): 149–156. PMID 8386360.
- Liaw CW, Grigoriadis DE, Lovenberg TW, De Souza EB, Maki RA (June 1997). "Localization of ligand-binding domains of human corticotropin-releasing factor receptor: a chimeric receptor approach". Molecular Endocrinology. 11 (7): 980–985. PMID 9178757.
- Timpl P, Spanagel R, Sillaber I, Kresse A, Reul JM, Stalla GK, et al. (June 1998). "Impaired stress response and reduced anxiety in mice lacking a functional corticotropin-releasing hormone receptor 1". Nature Genetics. 19 (2): 162–166. S2CID 20336316.
- Perone MJ, Murray CA, Brown OA, Gibson S, White A, Linton EA, et al. (July 1998). "Procorticotrophin-releasing hormone: endoproteolytic processing and differential release of its derived peptides within AtT20 cells". Molecular and Cellular Endocrinology. 142 (1–2): 191–202. S2CID 10621100.
- Willenberg HS, Bornstein SR, Hiroi N, Päth G, Goretzki PE, Scherbaum WA, et al. (March 2000). "Effects of a novel corticotropin-releasing-hormone receptor type I antagonist on human adrenal function". Molecular Psychiatry. 5 (2): 137–141. PMID 10822340.
- Saeed B, Fawcett M, Self C (February 2001). "Corticotropin-releasing hormone binding to the syncytiotrophoblast membranes". European Journal of Clinical Investigation. 31 (2): 125–130. S2CID 42612842.
External links
Media related to Corticotropin releasing hormone at Wikimedia Commons- Overview of all the structural information available in the PDB for UniProt: P06850 (Corticoliberin) at the PDBe-KB.
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