Inhibition of Adrenal Corticosteroid Synthesis by Aminoglutethimide: Studies of the Mechanism of Action1

Abstract

Amino-glutethimide inhibits corticosterone synthesis by the rat adrenal cortex both in vivo and in vitro. In intact rats the decrease in corticosterone production is accompanied by an increase in plasma ACTH. In the presence of endogenous or exogenous ACTH, amino-glutethimide causes marked accumulation of adrenal cholesterol. These observations, plus the fact that amino-glutethimide does not impair the conversion of pregnenolone to corticosterone, indicate that the drug inhibits the conversion of cholesterol to pregnenolone. Aminoglutethimide administration results in adrenal enlargement, an effect that appears to be partly due to cholesterol accumulation and partly due to the adrenal growth-promoting effect of increased endogenous ACTH.