Effect of dihydrotestosterone on rat liver alcohol dehydrogenase activity

Castration was previously demonstrated to result in an increase in liver alcohol dehydrogenase and in rates of ethanol elimination in male rats. In this study, the effect of dihydrotestosterone, which is a more potent androgen than testosterone in the rat, was determined on liver alcohol dehydrogenase and ethanol elimination in the castrated rat. Dihydrotestosterone was found to be a substrate of liver alcohol dehydrogenase in the reductive direction and a competitive inhibitor of ethanol oxidation by the enzyme. Also, the administration of a single dose of dihydrotestosterone inhibited liver alcohol dehydrogenase 4 hr after the injection, but this effect was not persistent at later intervals following injection. This transient in vivo inhibition of liver alcohol dehydrogenase was associated with a delay in ethanol elimination. The microsomal ethanol-oxidizing enzyme system was found to play no role in the changes in ethanol elimination observed after castration and dihydrotestosterone administration since its activity remained unchanged. These studies provide further evidence of an effect of androgenic steroids on liver alcohol dehydrogenase activity and ethanol metabolism.