Finasteride blocks progesterone synthesis in MA-10 Leydig tumor cells.
The 5 alpha-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 3 beta-hydroxysteroid dehydrogenase delta 5-->delta 4 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.
Freeman
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Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City 73104.
Gocze
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Porpaczy
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D003994:Bucladesine / Q000494:pharmacology; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000037:antagonists & inhibitors; D002849:Chromatography, Gas; D003470:Culture Media; D000242:Cyclic AMP / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018120:Finasteride / Q000494:pharmacology*; D006888:Hydroxycholesterols / Q000494:pharmacology; D007984:Leydig Cell Tumor / Q000378:metabolism* / Q000473:pathology; D009994:Osmolar Concentration; D011374:Progesterone / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D003470:Culture Media; D006888:Hydroxycholesterols; C003585:22-hydroxycholesterol; D011374:Progesterone; D018120:Finasteride; D003994:Bucladesine; D000242:Cyclic AMP; D002786:Cholesterol Side-Chain Cleavage Enzyme