Effects of cholesterol side chain cleavage inhibitors on 11 beta-hydroxylation: linkage of mitochondrial oxygenase systems.

Potent inhibitors of cholesterol side chain cleavage were tested for inhibition of 11 beta-hydroxylation of 11-deoxycortisol by bovine adrenal cortex mitochondria. Compounds which inhibited 11 beta-hydroxylation were metyrapone, 4-phenylimidazole, 1-benzylimidazole, 17 beta-ureido - 1, 4- androstadien-3-one. SU-8000, 4-methylaminoglutethimide, and 20 alpha-hydroxycholestrol. Compounds which did not inhibit 11 beta-hydroxylation at concentrations of 0.5 mM were d-aminoglutethimide tartrate, 1-aminoglutethimide tartrate, N-methylaminoglutethimide, 16 alpha-methylpregnenolone, 16 beta-methylpregnenolone, 20-tolylpregnenediol, 16 alpha-chloropregnenolone-3-acetate, 16 alpha-benzyloxpregnenolone-3-acetate and cyanoketone. The results obtained indicate that aminoglutethimide and its congeners, the 16-halogenated and 16-benzoylated derivatives of pregnenolone and cyanoketone are specific inhibitors of cholesterol side chain cleavage enzyme. The two mitochondrial steroid oxyganase systems are linked through their competition for a single electron source.