Inhibition of testosterone biosynthesis by ethanol: multiple sites and mechanisms in dispersed Leydig cells.

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Widenius TV, Orava MM, Vihko RK, Ylikahri RH, Eriksson CJ

Inhibition of testosterone biosynthesis by ethanol: multiple sites and mechanisms in dispersed Leydig cells.

J Steroid Biochem. 1987 Aug;28(2):185-8.

PubMed ID

3476810 [ View in PubMed

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Abstract

Isolated rat Leydig cells were incubated for 2 h in sealed polycarbonate tubes under O2/CO2 atmosphere with 10 mIU/ml human chorionic gonadotropin. 20 mmol/l ethanol reduced the concentration of testosterone (16%, P less than 0.025); raised the concentrations of pregnenolone (60%, P less than 0.001), androstenedione (86%, P less than 0.001) and dehydroepiandrosterone (81%, P less than 0.001); but did not change concentrations of progesterone and 17 alpha-hydroxyprogesterone in the incubation medium. Ethanol also raised the lactate/pyruvate ratio in the Leydig cell suspension. 4-Methylpyrazole (0.5 mmol/l) abolished the ethanol-induced changes. The present results suggest that ethanol inhibits testosterone synthesis in isolated rat Leydig cells at the pregnenolone-to-testosterone pathway by inhibiting 3 beta-hydroxy-5-ene-steroid dehydrogenase/5-ene-4-ene-isomerase catalyzed reactions and the conversion of androstenedione to testosterone. These inhibitions are caused by consequences of ethanol metabolism. A likely mechanism for the former inhibition is that the increase in the NADH/NAD+ ratio in Leydig cells leads to inhibition of reactions catalyzed by 3 beta-hydroxy-5-ene-steroid dehydrogenase/5-ene-4-ene isomerase, but the inhibition mechanism operating at the androstenedione-to-testosterone step remains to be characterized.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
NADH	3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1	Protein	Humans	Unknown	Not Available	Details
NADH	3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2	Protein	Humans	Unknown	Not Available	Details