For over 25 years, investigators searched for the elusive hypothalamic hormone corticotrophin-releasing factor, hypothesized to stimulate the pituitary release of ACTH. Finally, in 1981, Vale et al. (1981) identified a 41-amino-acid peptide that potently and specifically promoted the release of ACTH from the pituitary corti-cotroph. Further work demonstrated that this peptide met the criteria established for a releasing hormone. Like other hypothalamic releasing hormones, corticotrophin-releasing hormone (CRH) and its receptors were found to have extrahypoth-alamic brain distribution (Olschowka et al., 1982; Schipper et al., 1983; Swanson et al., 1983). From results of initial studies, it was hypothesized that CRH systems play an integrative role in an organism’s response to stress.
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