Demonstration of a functional blood-testis barrier to acetaldehyde. Evidence for lack of acetaldehyde effect on ethanol-induced depression of testosterone in vivo.
In vitro studies have shown that acetaldehyde is a more potent inhibitor of testicular steroidogenesis than ethanol. The present study examined the in vivo role of acetaldehyde in ethanol-induced reduction of testosterone by (1) determining the levels of acetaldehyde to which the testes were exposed subsequent to acute ethanol administration to mice; and (2) examining the effect of ethanol on testosterone in animals subsequent to drug pretreatment which decreased or increased ethanol-derived acetaldehyde. Ethanol-induced (3 g/kg) depression of testosterone was dependent upon gonadotropin stimulation. The increase in hCG-induced testosterone was suppressed (P less than 0.01) in ethanol- as compared to saline-treated animals [39.8 +/- 2.6 (S.E.M.) vs 28.1 +/- 2.3 ng/ml]. Pargyline (100 mg/kg) or cyanamide (8.4 mg/kg) increased (P less than 0.05) plasma and testicular acetaldehyde, while having no effect on the testosterone response to ethanol. Similarly, 4-methylpyrazole (25 mg/kg) reduced blood and testicular acetaldehyde to nondetectable levels, while having no effect on testosterone. Testicular acetaldehyde was lower (P less than 0.001) than plasma levels (14 +/- 2 vs 2.0 +/- 0.2 microM). This functional blood-testis barrier to acetaldehyde could be explained by testicular aldehyde dehydrogenases in the mitochondria (Km for acetaldehyde = 1.5 microM) and in the cytosol (Km = 123 microM) whose maximal activities totaled to more than 25-fold greater than that of testicular alcohol dehydrogenase (ADH). ADH was concentrated in the Leydig cells, while aldehyde dehydrogenase was evenly distributed in the testis. Ethanol prevented further hCG-induced rises in testosterone rather than inhibiting testosterone production to below pre-ethanol values. The above data argue against a significant role of acetaldehyde in the in vivo response of testosterone to ethanol. Ethanol appears to impair gonadotropin-testicular receptor interaction in vivo.
D000079:Acetaldehyde / Q000378:metabolism*; D000444:Aldehyde Dehydrogenase / Q000032:analysis; D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003484:Cyanamide / Q000494:pharmacology; D000431:Ethanol / Q000378:metabolism / Q000633:toxicity*; D000077604:Fomepizole; D008297:Male; D051379:Mice; D010293:Pargyline / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D013737:Testis / Q000187:drug effects / Q000378:metabolism*; D013739:Testosterone / Q000032:analysis*
D006063:Chorionic Gonadotropin; D011720:Pyrazoles; D000431:Ethanol; D013739:Testosterone; D003484:Cyanamide; D000077604:Fomepizole; D010293:Pargyline; D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde