Inhibition of testosterone production by rat Leydig cells with ethanol and acetaldehyde: prevention of ethanol toxicity with 4-methylpyrazole.
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 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. These studies suggest that ethanol per se may not directly inhibit testosterone biosynthesis. Rather, it would appear that acetaldehyde, the first product of ethanol metabolism, may be responsible for the toxic effects of ethanol upon Leydig cells at least in vitro.
D000079:Acetaldehyde / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D003864:Depression, Chemical; D000431:Ethanol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000077604:Fomepizole; D066298:In Vitro Techniques; D007984:Leydig Cell Tumor; D007985:Leydig Cells / Q000378:metabolism*; D008297:Male; D009374:Neoplasms, Experimental; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D013739:Testosterone / Q000096:biosynthesis*
D011720:Pyrazoles; D000431:Ethanol; D013739:Testosterone; D000077604:Fomepizole; D000079:Acetaldehyde