Effect of chronic ethanol feeding on testicular content of enzymes required for testosteronogenesis.
Ethanol is a known inducer of microsomal enzymes as well as a testicular toxin. In order to evaluate the effect of chronic ethanol ingestion upon the microsomal enzymes required for testosterone synthesis, we examined the activity of four testicular enzymes (3 beta-hydroxysteroid dehydrogenase/isomerase, 17 alpha-hydroxylase, 17,20-lyase, and 17 beta-hydroxysteroid dehydrogenase) in 14 pairs of adult chronic alcohol-fed rats and their age-matched isocaloric controls. Ethanol feeding enhanced the activity of 17,20-lyase when expressed as either activity/mg of protein (p less than 0.05) or activity/g of testis (P less than 0.025). Similarly, the activity of 17 alpha-hydroxylase was increased in testes of the alcohol-fed animals (p less than 0.025) compared to controls. In contrast, chronic ethanol feeding reduced total activity of 3 beta-hydroxysteroid dehydrogenase/isomerase in alcohol-fed animals (p less than 0.05) compared to controls. No effect of ethanol feeding was seen on activity of 17 beta-hydroxysteroid dehydrogenase. Based upon these studies we conclude that chronic ethanol ingestion (1) increases testicular 17 alpha-hydroxylase and 17,20-lyase and (2) reduces 3 beta-hydroxysteroid dehydrogenase/isomerase in rat testicular microsomes. Therefore, we would propose that the major effect of chronic ethanol ingestion upon the enzymes required for testosterogenesis is the reduction of 3 beta-hydroxysteroid dehydrogenase/isomerase activity, the rate limiting step in sex steroid production from pregnenolone.