Effect of activin A on dehydroepiandrosterone and testosterone secretion by primary immature porcine Leydig cells.
In the present study, we evaluated the effect of the homodimer activin A on immature porcine Leydig cell functions in primary culture. Activin A (0.5-100 ng/ml) reduced hCG-stimulated dehydroepiandrosterone (DHEA) accumulation in a dose- and time-dependent manner, with a maximal inhibitory effect (58% decrease) at 20 ng/ml (8 x 10(-10) M). Activin A was found not to control steroidogenesis, either through a modulation of the gonadotropin LH/hCG binding or low-density lipoprotein cholesterol binding and internalization. However, activin A significantly decreased pregnenolone (p less than 0.002) and DHEA (p less than 0.001) formation (evaluated in the presence of 10(-5) M of WIN 24540, an inhibitor of 3 beta-hydroxysteroid dehydrogenase/isomerase [3 beta-HSDI]activity) in Leydig cells maximally stimulated with hCG (3 ng/ml, 3 h) or incubated in the presence of 22R-hydroxycholesterol (5 micrograms/ml, 2 h). These findings indicate that activin A probably exerts a partial inhibitory effect on cholesterol side-chain cleavage cytochrome P450 (P450scc) activity. On the other hand, activin A significantly (p less than 0.001) enhanced the conversion of exogenous pregnenolone and DHEA (500 ng/ml) but not of progesterone and androstenedione (500 ng/ml) into testosterone, suggesting that activin A potentially enhances 3 beta-HSDI activity in Leydig cells. Activin A action on 3 beta-HSDI activity was found to be closely related to that of transforming growth factor-beta 1 (TGF beta 1), since both activin A (20 ng/ml) and TGF beta 1 (2 ng/ml) induced a comparable and non-additive increase in 3 beta-HSDI activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Mauduit
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INSERM CJF n. 90-08, Hôpital Sainte Eugénie, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France.
Chauvin
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MA
de Peretti
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Morera
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Benahmed
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D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000378:metabolism; D028341:Activins; D000818:Animals; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000378:metabolism*; D013196:Dihydrotestosterone / Q000031:analogs & derivatives / Q000494:pharmacology; D006888:Hydroxycholesterols / Q000494:pharmacology; D007265:Inhibins / Q000494:pharmacology*; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011284:Pregnenolone / Q000378:metabolism; D013552:Swine; D013739:Testosterone / Q000378:metabolism*
D006063:Chorionic Gonadotropin; D006888:Hydroxycholesterols; D013196:Dihydrotestosterone; D028341:Activins; D013739:Testosterone; D003687:Dehydroepiandrosterone; D007265:Inhibins; D011284:Pregnenolone; D003577:Cytochrome P-450 Enzyme System; D015096:3-Hydroxysteroid Dehydrogenases; C009954:trilostane