Corticotropin-release inhibitory factor. Evidence for dual stimulatory and inhibitory hypothalamic regulation over adrenocorticotropin secretion and biosynthesis

Dennis Engler, Jun Ping Liu, Iain J. Clarke, John W. Funder

Research output: Contribution to journalReview ArticleResearchpeer-review

11 Citations (Scopus)


The hypothalamus is currently thought to stimulate the synthesis and secretion of ACTH uniquely by secreting neuropeptides into the hypophysial-portal circulation, of which the most important are CRH and arginine vasopressin. However, analysis of the effects of pituitary isolation on the pituitary-adrenal axis in a variety of species suggests that the hypothalamus exerts both stimulatory and inhibitory regulation over ACTH secretion and POMC biosynthesis, and that the inhibitory control is dominant. Because none of the currently known inhibitory factors in the hypophysial-portal circulation consistently decreases basal ACTH secretion and POMC mRNA levels in normal anterior pituitary cells, it is suggested that this inhibition is mediated by a currently unidentified hypothalamic substance, presumably a neuropeptide, which we have termed corticotropin-release inhibitory factor (CRIF). The possible roles in clinical medicine of agonists and antagonists of this putative CRIF are discussed.

Original languageEnglish
Pages (from-to)272-283
Number of pages12
JournalTrends in Endocrinology and Metabolism
Issue number7
Publication statusPublished - 1 Jan 1994
Externally publishedYes

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