Ethanol directly inhibits delta 5-3 beta-hydroxysteroid dehydrogenase-isomerase activity in rat testis interstitial...

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.