Corticotropin-releasing hormone

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Corticotropin releasing hormone
PDB rendering based on 1go9.
Identifiers
Symbol(s) CRH; CRF
External IDs OMIM: 122560 MGI: 88496 Homologene: 599
RNA expression pattern

More reference expression data

Orthologs
Human Mouse
Entrez 1392 12918
Ensembl ENSG00000147571 ENSMUSG00000049796
Uniprot P06850 Q14AA2
Refseq NM_000756 (mRNA)
NP_000747 (protein) 		NM_205769 (mRNA)
NP_991338 (protein)
Location Chr 8: 67.25 - 67.25 Mb Chr 3: 19.89 - 19.89 Mb
Pubmed search [1] [2]

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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 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).

ά-helical CRH-(9--41) acts as a CRH antagonist[1].

Psychopharmacy

The CRH-1 receptor antagonist pexacerfont is currently under investigation for the treatment of Generalized Anxiety Disorder in women[1]. 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.[1]

Role in parturition

CRH is also synthesized by the placenta and seems to determine the duration of pregnancy[1].

Levels rise towards birth and current theory suggests three roles of CRH in parturition.[1]
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.[1]

Structure

The 41-amino acid sequence of CRH was first discovered in sheep by Vale et al in 1981[1]. Its full sequence is

SQEPPISLDLTFHLLREVLEMTKADQLAQQAHSNRKLLDIA

See also

References

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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
v • d • e
Endocrine system: hormones/endocrine glands (Peptide hormones, Steroid hormones)
Hypothalamic-pituitary Hypothalamus: TRH, CRH , GnRH, GHRH, somatostatin, dopamine - Posterior pituitary: vasopressin, oxytocin - Anterior pituitary: α (FSH, LH, TSH), GH, prolactin, POMC (ACTH, MSH, endorphins, lipotropin)
Adrenal axis Adrenal medulla: epinephrine, norepinephrine - Adrenal cortex: aldosterone, cortisol, DHEA
Thyroid axis Thyroid: thyroid hormone (T3 and T4) - calcitonin - Parathyroid: PTH
Gonadal axisTestis: testosterone, AMH, inhibin - Ovary: estradiol, progesterone, inhibin/activin, relaxin (pregnancy)
Other end. glands Pancreas: glucagon, insulin, somatostatin - Pineal gland: melatonin
Non-end. glands Placenta: hCG, HPL, estrogen, progesterone - Kidney: renin, EPO, calcitriol, prostaglandin - Heart atrium: ANP - Stomach: gastrin, ghrelin - Duodenum: CCK, GIP, secretin, motilin, VIP - Ileum: enteroglucagon - Adipose tissue: leptin, adiponectin, resistin - Thymus: Thymosin - Thymopoietin - Thymulin - Skeleton: Osteocalcin - Liver/other: Insulin-like growth factor (IGF-1, IGF-2)
Target-derivedNGF, BDNF, NT-3
v • d • e
Peptides: neuropeptides
HypothalamicSomatostatin - CRH - GnRH - GHRH - Orexins - TRH - POMC (ACTH, MSH, Lipotropin)
Gastrointestinal hormonesCholecystokinin - Gastric inhibitory polypeptide - Gastrin - Motilin - Secretin - Vasoactive intestinal peptide
Other hormonesVasopressin - Calcitonin -
OtherAngiotensin - Bombesin/Neuromedin B - Calcitonin gene-related peptide - Carnosine - Delta sleep-inducing peptide - FMRFamide - Galanin - Gastrin releasing peptide - Kinins (Bradykinin, Tachykinins ) - Neuromedin (B, N, U) - Neuropeptide Y - Neurophysins - Neurotensin - Opioid peptide - Pancreatic polypeptide - Pituitary adenylate cyclase activating peptide
cs:Kortikoliberin

de:Corticotropin-releasing Hormone dv:ކޯޓިކޯޓްރޮޕިން ރިލީސިންގ ހޯރމޯންfr:Corticolibérine it:Ormone di liberazione della corticotropina mk:Адренокортикотропен ослободувачки хормон nl:Corticotropin-releasing hormone ja:副腎皮質刺激ホルモン放出ホルモンsl:Kortikoliberin sv:Kortikotropinfrisättande hormon


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Acknowledgement and Attribution Regarding Sources of Content

Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .

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