Angiotensin II induces the release of 19-hydroxyandrostenedione in man.

Plasma concentrations of 19-hydroxyandrostenedione [19-hydroxy-4-androstene-3,17-dione (19-OH-A-dione)], which we reported to be an amplifier of the action of aldosterone on the basis of results obtained in bioassays using adrenalectomized rats, were measured in man using a specific and sensitive RIA. Plasma 19-OH-A-dione concentrations (mean +/- SE) in normal subjects were 56 +/- 4 pg/ml in men and 51 +/- 4 pg/ml in women. Plasma 19-OH-A-dione rose significantly during ACTH stimulation and declined significantly during dexamethasone suppression. Plasma 19-OH-A-dione levels in the adrenal vein were an order of magnitude higher than those in the inferior vena cava. These results demonstrate that 19-OH-A-dione is directly secreted by the adrenal cortex and that its secretion is under the control of ACTH. As the action of 19-OH-A-dione may be closely related to that of aldosterone, the response of 19-OH-A-dione to angiotensin II infusion was evaluated and compared with that of aldosterone. During the infusion of graded doses (0.5-4.0 ng/kg . min) of angiotensin II, plasma 19-OH-A-dione increased significantly after the infusion of angiotension II at rates of 1.0 and 2.0 ng/kg . min. It then declined after the infusion of angiotensin II at a rate of 4.0 ng/kg . min. In contrast, plasma aldosterone did not increase significantly until the infusion rate reached 4.0 ng/kg . min. These results indicate that the secretion of 19-OH-A-dione is under the control of angiotensin II. Similar changes in 19-OH-A-dione and aldosterone were found during postural changes. In those subjects who had a small increase in plasma aldosterone when they were upright, 19-OH-A-dione significantly increased. In contrast, in those subjects who had a large increase in plasma aldosterone when upright, 19-OH-A-dione significantly declined. These results suggest that a small elevation of endogenous angiotensin II induces an elevation of plasma 19-OH-A-dione, and a sharp increase in endogenous angiotensin II induces an increase in plasma aldosterone and a decline in plasma 19-OH-A-dione. As angiotensin II stimulated the release of 19-OH-A-dione when the secretion of ACTH was suppressed, angiotensin II acted directly on the adrenal cortex. 19-OH-A-dione is a newly recognized biologically active adrenal C19 steroid which is regulated by both ACTH and the renin-angiotensin system in man.