INHIBITION OF ALDOSTERONE SECRETION AND MODIFICATION OF ELECTROLYTE EXCRETION IN MAN BY A CHEMICAL INHIBITOR OF 11β-HYDROXYLATION*†

Abstract

2-Methyl-l,2-bis-(3-pyridyl)-l-propanone SU-4885 is a potent inhibitor of 11/[beta]-hydroxylatlon of steroids in man. As a result, SU-4885 interferes with adrenocortical synthesis and secretion of 3 major adrenal steroids[long dash]cortisol, corticosterone, and aldosterone. Since cortisol controls ACTH release, administration of SU-4885 gives rise to a compensatory increase in ACTH. In the presence of inhibition of Il[beta]-hydroxylation, ACTH promotes secretion of desoxycorticosterone and compound S, the former a potent mineralocorticoid. The net effect of SU-4885 on electrolyte excretion is the algebraic sum of its DOC-promoting and aldosterone-inhibition activities.