Angiotensin stimulates both early and late steps in aldosterone biosynthesis in isolated bovine glomerulosa cells

Abstract

The present study was designed to examine the effect of angiotensin on both the early and the late phases of aldosterone biosynthesis. In order to isolate the early phase (the formation of pregnelone). it was necessary to identify an agent that would inhibit the 3β-hydroxysteroid dehydrogenase, 4–5 eneisomerase enzyme system which facilitates the conversion of pregnenolone to progesterone. Such an agent was found in trilostane. Treatment of zona glomerulosa cells with trilostane resulted in accumulation of pregnenolone, and the addition of angiotensin increased the accumulation of pregnenolone still further. This observation demonstrates that angiotensin stimulates aldosterone biosynthesis at a point prior to pregnenolone formation. The late phase of aldosterone biosynthesis was isolated by using aminoglutethimide to inhibit the formation of pregnenolone by cells of the zona glomerulosa. Aldosterone was formed when aldosterone precursors occurring in the biosynthetic pathway from pregnenolone onward were added. When angiotensin was added along with deoxycorticosterone, the conversion of deoxycorticosterone to aldosterone was enhanced ( P < 0.05). This observation demonstrates that angiotensin stimulates aldosterone formation at a point distal to deoxycorticosterone formation. Thus, angiotensin stimulates aldosterone biosynthesis at at least 2 independent points, one early and one late in the biosynthetic pathway.