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 potassium can modulate aldosterone biosynthesis. However, the site of action of potassium on the aldosterone biosynthetic pathway has not been definitively established. This study was designed to examine in vitro the effects of potassium on the isolated early phase and the isolated late phase of aldosterone biosynthesis in adrenal cell suspensions. When the potassium concentration was increased in glomerulosa cell suspensions from 0 to 6 mEq/liter, a significant increase in aldosterone production occurred (P < 0.01). However, when the potassium concentration was increased from 6 to 12 mEq/liter, changes observed 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, therefore, to aldosterone. Increasing the potassium concentration of trilostane- treated glomerulosa cell suspensions either from 0 to 6 mEq/liter or from 6 to 12 mEq/liter significantly increased pregnenolone accumulation (P < 0.01 and 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 potassium concentration of 6 mEq/liter than at zero potassium (P < 0.01), but the conversion was significantly less at a potassium concentration of 12 mEq/liter than at 6 mEq/liter (P < 0.01). These observations indicate that as the potassium concentration is increased from 0 to 6 mEq/liter, both the early and late phases of aldosterone biosynthesis are independently stimulated, resulting in increased aldosterone production. However, when the potassium concentration is increased from 6 to 12 mEq/liter, opposing effects of potassium on the two phases of aldosterone biosynthesis occur, and changes in net aldosterone production are small and variable. © 1978 by The Endocrine Society.