Corticotropin-releasing hormone (CRH), originally named corticotropin-releasing factor (CRF), and also called corticoliberin, is a polypeptidehormone 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.
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.
The CRH-1 receptor antagonist pexacerfont is currently under investigation for the treatment of Generalized Anxiety Disorder in women.
Role in parturition
CRH is also synthesized by the placenta and seems to determine the duration of pregnancy.
The 41-amino acid sequence of CRH was first discovered in sheep by Vale et al in 1981. Its full sequence is
^ 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
^ 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)
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