Ethanol directly inhibits delta 5-3 beta-hydroxysteroid dehydrogenase-isomerase activity in rat testis interstitial cells.
Acute ethanol exposure has been demonstrated to inhibit testosterone synthesis both in vivo and in vitro; however, the precise step(s) affected is controversial. Using intact collagenase-dispersed interstitial cells or 10,000 xg supernatants of interstitial cell homogenates, studies were undertaken to determine whether ethanol specifically inhibited delta 5-3 beta-hydroxysteroid dehydrogenase-isomerase activity. In both cellular preparations, varying concentrations of ethanol (2.2 - 652 mM) inhibited this enzyme activity. Because alcohol dehydrogenase activity was identified specifically in Leydig cells and because the inhibition of delta 5-3 beta-hydroxysteroid dehydrogenase-isomerase activity by concentrations of ethanol normally observed in circulation of alcoholic men (2.2 - 65 mM) could be reversed by saturating concentrations of NAD+ (0.2 mM) or by 4-methylpyrazole (2 mM), these results suggest that the mechanism of this inhibition is by limitation of available cofactor.
D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000818:Animals; D000431:Ethanol / Q000494:pharmacology*; D000077604:Fomepizole; D066298:In Vitro Techniques; D007985:Leydig Cells / Q000187:drug effects; D008297:Male; D009243:NAD / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013737:Testis / Q000166:cytology / Q000201:enzymology*
D011720:Pyrazoles; D009243:NAD; D000431:Ethanol; D000077604:Fomepizole; D015096:3-Hydroxysteroid Dehydrogenases; D000429:Alcohol Oxidoreductases; C031954:delta(5)-3 beta-hydroxysteroid dehydrogenase