Inhibition of steroidogenesis in cultured Leydig tumor cells by 22-amino-23,24-bisnor-5-cholen-3 beta-O1 and (20R) 20-phenyl-5-pregnene-3 beta,20-diol.
Using the cholesterol side-chain cleavage enzyme purified from bovine adrenals, we have previously shown that 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 studies presented herein were designed to characterize the effects of these new inhibitors on steroid production by intact cells. Using cultured Leydig tumor cells, we compared the effects of 22-ABC, 20-PPD, and aminoglutethimide (a well-known inhibitor of the cholesterol side-chain cleavage enzyme) on hormone-stimulated steroidogenesis. Our results show that these compounds inhibit steroid production in a dose-dependent manner and that 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.
D000616:Aminoglutethimide / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007984:Leydig Cell Tumor / Q000378:metabolism*; D008297:Male; D011283:Pregnenes / Q000494:pharmacology*; D011284:Pregnenolone / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism; D013736:Testicular Neoplasms / Q000378:metabolism*; D013997:Time Factors
C012486:20-phenyl-5-pregnene-3 beta,20-diol; D006063:Chorionic Gonadotropin; D011283:Pregnenes; D000616:Aminoglutethimide; D011374:Progesterone; C006517:22-aminocholesterol; D011284:Pregnenolone; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol