Transfer of deuterium from [1,1-2H2]ethanol to steroids and organic acids in the rat testis

Abstract

Rats were given [1,1-2H2]ethanol in a single dose, and the 2H content was determined in testicular steroids and in organic acids of low molecular mass in the testis, liver and blood. The acids were quantified by capillary gas chromatography/mass spectrometry of t-butyldimethylsilyl derivatives with [2H4]lactate as internal standard. In addition to lactate, pyruvate, 3-hydroxybutyrate and acids of the tricarboxylic acid cycle, the testis was shown to contain 2-hydroxybutyrate, 2-hydroxy-2-methylbutyrate, 2-hydroxyisohexanoate and glycerate. No 2H was found in pregnenolone, 5-androstene-3 beta,17 beta-diol or testosterone, whereas the abundance of monodeuterated molecules of 5 alpha-androstane-3 alpha,17 beta-diol and its 3 beta-isomer were 7.6% and 11.2% respectively. The abundance of monodeuterated lactate was 7.0% in the testis and 5.3% in the blood. The other acids were less labelled but 3-hydroxybutyrate had a higher 2H content in the testis (3.1%) than in the liver. These results support the contention that ethanol is oxidized in an alcohol dehydrogenase-catalysed reaction in testis in vivo and that the acute inhibition of the testosterone production is due at least partly to a redox effect. The labelling and increased concentration of 3-hydroxybutyrate in the testis indicate that a change in the mitochondrial redox state might be involved.

Fifty years with bile acids and steroids in health and disease

“…The results showed that ethanol increased the ratios between 3β-hydroxy-∆ 5 -/3oxo-∆ 4 -steroid couples, compatible with an inhibition of testosterone biosynthesis. Later studies with [1,1-2 H 2 ]ethanol indicated that this was a direct effect of testicular ethanol metabolism on the redox state, not mediated by lactic acid from the liver (98). Thus, it appears that ethanol-induced redox changes can be of endocrinological importance both via effects on the metabolism and the biosynthesis of steroid hormones.…”

Acutely Administered Ethanol Participates in Testosterone Synthesis and Increases Testosterone in Rat Brain

“…Martel et al concluded that the "widespread distribution of 17␤-HSD in rat clearly indicates the importance of this enzyme in peripheral sex steroid formation." Norsteen-Hoog et al (1992) investigated the transfer of deuterium from 1,1-dideuteroethanol to steroids in isolated rat testis; no deuterium was found in pregnenolone or testosterone. The transfer of deuterium from 1,1-dideuteroethanol to testosterone requires a change in the redox state of the oxidized nicotinamide adenine dinucleotide phosphate system, as shown in Fig.…”