Mevinolin (Lovastatin) Inhibits Androstenedione Production by Porcine Ovarian Theca Cells at the Level of the 17α-Hydroxylase:C-17,20-Lyase Complex*†

作者: HEIDI ENGELHARDT , R. E. GORE-LANGTON , D.T. ARMSTRONG

DOI: 10.1210/ENDO-124-5-2297

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摘要: Mevinolin, putatively a specific inhibitor of 3- hydroxy-3-methylglutaryl coenzyme-A reductase, was used to assess the contribution de novo synthesized cholesterol androgen production by ovarian thecal cells in vitro. Enzymatically dispersed from 6-mm follicles prepubertal gilts were incubated at 150,000 cells/ml with maximally effective dose LH (250 ng/ml) for 24 h. Mevinolin (3-50 μM) caused dose-dependent inhibition androstenedione production. Addition 25-hydroxycholesterol (0.025-25 failed restore levels seen absence mevinolin, suggesting an additional site action mevinolin beyond 3-hydroxy-3-methylglutaryl coenzyme reductase. The this inhibitory effect determined measuring steroid products formed presence relevant precursors. (12 inhibited 17α-hydroxyprogesterone progesterone and that 17α-hydroxyprogesterone, while 25...

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