FINASTERIDE BLOCKS PROGESTERONE SYNTHESIS IN MA-10 LEYDIG TUMOR-CELLS

The 5alpha-reductase inhibitor, finasteride, inhibits progesterone synthesis in the MA-10 Leydig tumor cells. Inhibition is dose-dependent with half maximal inhibition occurring at 10 ng/ml, a concentration significantly less than serum concentrations detected in finasteride-treated patients. Experiments to localize the site of inhibition by this compound revealed that the 3beta-hydroxysteroid dehydrogenase DELTA5-->DELTA4, isomerase enzyme was not blocked by finasteride, but that cholesterol side-chain cleavage was inhibited. Thus, both dibutyryl-cAMP-stimulated and 22-hydroxycholesterol-stimulated steroidogenesis were inhibited by finasteride. This effect of finasteride to block cholesterol side-chain cleavage may be species-specific. Inhibition is readily detected in the mouse-derived MA-10 cells; however, human granulosa cell steroidogenesis is finasteride-insensitive while rat Leydig cell steroidogenesis is only minimally effected by finasteride.