CORTICOTROPIN-RELEASE INHIBITORY FACTOR - EVIDENCE FOR DUAL STIMULATORY AND INHIBITORY HYPOTHALAMIC REGULATION OVER ADRENOCORTICOTROPIN SECRETION AND BIOSYNTHESIS

The hypothalamus is currently thought to stimulate the synthesis and s ecretion of ACTH uniquely by secreting neuropeptides into the hypophys ial-portal circulation of which the most important ave CRH and arginin e vasopressin. However analysis of the effects of pituitary isolation on the pituitary-adrenal axis in a variety of species suggests that th e hypothalamus exerts both stimulatory and inhibitory regulation over ACTH secretion and POMC biosynthesis, and that ate 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, if is suggested that this inhibition is mediated by a currently unidentif ied hypothalamic substance, presumably a neuropeptide, which we have t ermed corticotropin-release inhibitory factor (CRIF). The possible rol es in clinical medicine of agonists and antagonists of this putative C RIF ave discussed.