REGULATION OF ADRENOCORTICAL FUNCTION BY VASOPRESSIN

Accumulating data obtained from various animal species indicate that v asopressin (AVP) participates in the regulation of adrenocortical func tion. AVP doubled aldosterone and cortisol secretion but did not affec t corticosterone secretion. Pharmacological studies indicate that the AVP receptors in the cortex belong to the V1 a subtype. Activation of V1 a receptors induces breakdown of membrane phosphoinositides, with s ubsequent accumulation of inositol phosphates and diacylglycerol. Thes e effects occur after receptor binding, G-protein activation and coupl ing to a specific phospholipase C. Inositol trisphosphate, transiently produced, induces a rapid release of Ca2+ from intracellular stores. Diacylglycerol activates protein kinase C, which, together with calciu m, is responsible for steroid secretion. The early events of AVP actio n are mediated by two types of G-proteins. One is coupled to phospholi pase C, and insensitive to pertussis toxin (probably G(q)/(11)) and a second one, which is inactivated by pertussis toxin (G(i) protein), is involved in the stimulation of calcium influx. This Ca2+ influx pathw ay is very important, as no steroidogenic effect of AVP could be obser ved when experiments were performed in a calcium-free medium or in per tussis toxin-treated cells. Besides the pituitary, the adrenal is also a source for AVP production. Indeed, AVP is synthesized and secreted by chromaffin cells either present in the medulla or scattered through out the cortex with a more prominent concentration in zona glomerulosa . AVP receptors are also present on chromaffin cells. However, in cont rast to AVP receptors in the cortex, these mainly belong to the V1b su btype, although V1 a receptors are also detected. The results summariz ed in this review conclusively indicate that AVP is one of the regulat ors of both cortex and medulla, an influence which may be mediated in part via pituitary AVP and in part via local production of AVP.