Effect of Chronic Alcohol Ingestion on the Biosynthesis of Steroids in Rat Testicular Homogenatein Vitro*

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Abstract
The activity and kinetics of Δ5-3β-dehydrogenase and 17α-hydroxylase, using labeled pregnenolone as substrate, were measured in gonadal homogenates from rats fed alcohol or isocalorically substituted carbohydrate for 40 days. There was no difference in the rate or reaction kinetics for either enzyme noted between control and alcohol-treated animals when the assays were carried out in the presence of saturating amounts of exogenous pyridine nucleotide cofactors. However, when exogenous cofactors were omitted from the reaction mixture, there was decreased activity of the Δ5-3β-dehydrogenase system and increased activity of the 17α-hydroxylase reaction. Furthermore, a cofactor-specific inhibiting effect on Δ5-3β-dehydrogenase activity by NADH and NADPH was found. Incubation of gonadal homogenates from the alcohol-treated animals with pyruvate or lactate (in the absence of exogenous cofactors) resulted in an increase and a decrease, respectively, in enzyme activity. These studies indicate that chronic alcohol use decreases gonadal Δ5-3β-dehydrogenase activity and that this is most likely due to an effect of the agent on the concentration and/or availability of pyridine nucleotide cofactors rather than to a direct effect on the enzyme. This phenomenon may account for the mechanism by which alcohol decreases testosterone secretion in these animals. (Endocrinology106: 1880, 1980)