The Effects of Potassium on Early and Late Steps in Aldosterone Biosynthesis in Cells of the Zona Glomerulosa*

Abstract

It has been clearly established that K can modulate aldosterone biosynthesis. The site of action of K on the aldosterone biosynthetic pathway has not been definitively established. This study was designed to examine in vitro the effects of K on the isolated early phase and the isolated late phase of aldosterone biosynthesis in adrenal cell suspensions. When the K concentration was increased in glomerulosa cell suspensions from 0 to 6 meq/l, a significant increase in aldosterone production occurred (P < 0.01). When the K concentration was increased from 6 to 12 meq/l, changes in aldosterone production were small and inconsistent. The early phase of aldosterone biosynthesis was then isolated, using trilostane to inhibit the conversion of pregnenolone to progesterone and to aldostane-treated glomerulosa cell suspensions either from 0-6 meq/l or from 6-12 meq/l significantly increased pregnenolone accumulation (P < 0.01 amd P < 0.01, respectively). The late phase of aldosterone biosynthesis was isolated using aminoglutethimide, which inhibits the conversion of cholesterol to pregnenolone. In aminoglutethimide-treated cell suspensions the conversion of corticosterone to aldosterone was significantly greater at a K concentration of 6 meq/l than at zero K (P < 0.01), but the conversion was significantly less at a K concentration of 12 meq/l than at 6 meq/l (P < 0.01). As the K concentration is increased from 0-6 meq/l both the early and late phases of aldosterone biosynthesis are independently stimulated, resulting in increased aldosterone production. When the K concentration is increased from 6-12 meq/l, opposing effects of K on the phases of aldosterone biosynthesis occur, and changes in net aldosterone production are small and variable.