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Corticotropin-releasing hormone




Corticotropin releasing hormone
PDB rendering based on 1go9.
Available structures: 1go9, 1goe
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]

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 production 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]

Contents

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[2].

Psychopharmacy

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

Role in parturition

CRH is also synthesized by the placenta and seems to determine the duration of pregnancy[4].

Structure

The 41-amino acid sequence of CRH was first discovered in sheep by Vale et al in 1981[5]. Its full sequence is

SQEPPISLDLTFHLLREVLEMTKADQLAQQAHSNRKLLDIA

See also

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

References

  1. ^ Entrez Gene: CRH corticotropin releasing hormone.
  2. ^ Santos, Javier, Paul R. Saunders, Nico P. M. Hanssen, Ping-Chang Yang, Derrick Yates, Jack A. Groot, and Mary H. Perdue. Corticotropin-releasing hormone mimics stress-induced colonic epithelial pathophysiology in the rat. Am. J. Physiol. 277 (Gastrointest. Liver Physiol. 40): G391-G399, 1999
  3. ^ http://www.clinicaltrials.gov/ct/show/NCT00481325?order=31
  4. ^ http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/H/Hypothalamus.html#CRH
  5. ^ Vale,W., Spiess,J., Rivier,C. and Rivier,J. Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin Science 213 (4514), 1394-1397 (1981)

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. 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. 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. 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. 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. 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. 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. 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. 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 - 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
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Corticotropin-releasing_hormone". A list of authors is available in Wikipedia.
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