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00019616-199707011-00002ArticleThe EndocrinologistThe Endocrinologist© Lippincott-Raven Publishers.7January 1997 p 3S–9SCorticotropin-Releasing Factor (CRF) Family of Ligands and Their ReceptorsArticle: PDF OnlyVale, Wylie Ph.D.; Vaughan, Joan; Perrin, Marilyn Ph.D.The Salk Institute, La Jolla, California 92037.Address correspondence to: Wylie Vale, Ph.D., The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037. Phone: 619–453–4100, ext. 1307. Fax: 619–552–1546; e-mail:[email protected] factor (CRF) was recognized biologically in the 1950s and was first isolated from ovine hypothalamus and characterized as a 41 amino acid peptide in 1981. Subsequently, rat and human CRF were identified and found to be identical to one another, while differing from ovine CRF by seven residues. A variety of experimental observations indicate that CRF is the key neuroregulator of the hypothalamic-pituitary-adrenal cortical (HPA) axis. The actions of CRF on adrenocorticotropic hormone (ACTH) secretion are potentiated by vasopressin and blunted by glucocorticoid negative feedback. The broad central and peripheral distribution of the peptide and its receptors supports the notion that CRF is an important local regulator within the central nervous, immune, and other systems. Further, CRF mediates numerous complementary stress-related endocrine, immune, autonomic, and behavioral responses.Antagonists of CRF, such as α-helical CRF or astressin, block many stress-induced physiologic and pathophysiologic responses in experimental animals, and perturbations of the CRF system or the HPA have been reported in human affective disorders. The effects of CRF within the central nervous system may be anatomically and temporally limited by a high-affinity binding protein (CRF-BP). The actions of CRF are mediated by seven transmembrane-domain G-protein-coupled receptors (CRF-R) derived from two genes (R1 and R2), each of which has alternative splice variants. We have identified a novel urotensin and CRF-like peptide, urocortin, in the rat brain and the human genome. Urocortin has a high affinity for CRF-R1 and R2 as well as for CRF-BP. Synthetic urocortin has potent biological actions on both CRF-R1 (pituitary ACTH release) as well as CRF-R2 (vasodilation, reduction of vascular permeability) mediated events. This novel peptide appears to be an endogenous ligand for CRF-type 2 receptors.<strong xmlns:mrws="">Corticotropin-Releasing Factor (CRF) Family of Ligands and Their Receptors</strong>Vale Wylie Ph.D.; Vaughan, Joan; Perrin, Marilyn Ph.D.Article: PDF OnlyArticle: PDF Only17p 3S-9S