Corticotrophin releasing factor may be modulated vasopressin

Abstract

CORTICOTROPHIN RELEASING FACTOR (CRF) was the first of the postulated hypothalamic factors controlling the release of hormones from the pituitary gland to be demonstrated biologically¹. However, it is extraordinary that after 24 years of research, techniques which have established the identity of the hypothalamic peptides involved in the release of thryotrophin, the gonadotrophins and growth hormone, have been unsuccessful when applied to the search for a factor responsible for adrenocorticotrophin (ACTH) release^2,3. Vasopressin invariably releases ACTH from the anterior pituitary, but its partial agonistic properties in vitro^4–6, its low potency in vivo⁷ and the isolation of active CRF fractions with little or no vasopressin activity^2,3,8,9 have led to its rejection as a physiological CRF^10,11. However, recent immunological and immunocytochemical findings have led to renewed interest in the role of vasopressin in ACTH release. High concentrations of immunoreactive vasopressin have been found in portal blood and a direct vasopressin-neurophysin containing axonal pathway to the hypophyseal portal system, which seems to be under the influence of the adrenal cortex, has been identified^12,13. Using a sensitive releasing factor bioassay system, the perfused isolated anterior pituitary cell column¹⁴, and various immunological techniques, we have presented evidence to support the idea that vasopressin plays a major part in control of ACTH release⁶, and we now report the existence of hypothalamic factors with weak, labile CRF activity which potentiate the CRF activity of vasopressin to give it full agonistic properties indistinguishable from crude extracts of rat stalk median eminence (SME). Thus we propose that CRF is vasopressin modulated by other hypothalamic factor(s) released into the hypothalamo-hypophyseal portal system.