Inhibition of Testosterone Production by Rat Leydig Cells with Ethanol and Acetaldehyde: Prevention of Ethanol Toxicity with 4‐Methylpyrazole

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Abstract
The toxic effects of ethanol and acetaldehyde on testosterone biosynthesis were examined in vitro using isolated Leydig cells prepared from adult rat testes. The ability of 4-methylpyrazole, an inhibitor of alcohol dehydrogenase. to prevent the toxic effects of ethanol on testosterone production was investigated. Ethanol was found to inhibit gonadotropin-stimulated testosterone production in a dose dependent fashion. Concentrations of ethanol (25 mg/100 ml), 1/4 the legal limit of intoxication in man, were shown to reduce testosterone levels by 44% as compared to the controls. Acetaldehyde at micromolar concentrations also inhibited testosterone biosynthesis. The addition of 4-methylpyrazole to the culture medium prevented the toxic effects of ethanol as determined by testosterone production. Ethanol per se may not directly inhibit testosterone biosynthesis. Acetaldehyde, the 1st product of ethanol metabolism, may be responsible for the toxic effects of ethanol upon Leydig cells at least in vitro.