Inhibition of Steroidogenesis in Cultured Leydig Tumor Cells by 22-Amino-23,24-Bisnor-5-Cholen-3β-Ol and (20R)20-Phenyl-5-Pregnene-3β,20-Diol*

Abstract
Using the cholesterol side-chain cleavage enzyme purified from bovine adrenals, 22-amino-23,24-bisnor-5-cholen-3-.beta.-ol (22-ABC) and (20R)20-phenyl-5-pregnene-3.beta.,20-diol (20-PPD) are potent competitive inhibitors of this enzyme. The effects of these new inhibitors on steroid production by intact cells were characterized. Using cultured Leydig tumor cells, the effects of 22-ABC, 20-PPD and aminoglutethimide (a well known inhibitor of the cholesterol side-chain cleavage enzyme) on hormone-stimulated steroidogenesis were compared. These compounds inhibit steroid production in a dose-dependent manner and 20-PPD and 22-ABC are about 100 and 4 times more active, respectively, than aminoglutethimide. In these cells, the inhibitory effects of the new compounds seem to be localized exclusively at the conversion of cholesterol to pregnenolone.