VASOPRESSIN STIMULATES STEROID-SECRETION IN HUMAN ADRENAL-GLANDS - COMPARISON WITH ANGIOTENSIN-II EFFECT

Autoradiographic experiments using iodinated vasopressin analog reveal ed the presence of specific vasopressin-binding sites in the human adr enal cortex (zona glomerulosa and zona fasciculata). These receptors e xhibited a good affinity for arginine vasopressin (3.3 nM), with class ical V-1a pharmacology and densities of 65 and 135 fmol/mg protein-enr iched membranes from zona glomerulosa and fasciculata, respectively. V asopressin receptors present in both glomerulosa and fasciculata cell- enriched primary cultures were coupled to phospholipase C (ED(50), 0.9 and 1.8 nM; maximal stimulation, 4.3- and 5.8-fold, respectively). Va sopressin also stimulated an increase in intracellular calcium through at least two distinct mechanisms: the mobilization of intracellular p ools via vasopressin-stimulated inositol phosphate accumulation and th e activation of calcium influx. In glomerulosa cell-enriched primary c ultures, vasopressin increased aldosterone secretion (ED(50), 0.4 nM; maximal stimulation, 2.5-fold) and was found to be as potent as angiot ensin-II in stimulating aldosterone secretion, phosphoinositide turnov er, and calcium mobilization. In fasciculata cells, vasopressin and an giotensin-II were also able to stimulate cortisol secretion and inosit ol phosphate accumulation. Moreover, perifusion experiments demonstrat ed that vasopressin was released from the adrenal medulla. Together, t hese results indicate that vasopressin can be considered a potent para crine modulator of adrenal steroid secretion in man.