The effects of ethanol and NAD+on the pregnenolone-to-testosterone pathway of testicular steroidogenesis in lysed Leydig cell preparations were investigated. Testosterone and four precursor steroids were determined by gas chromatography/mass spectrometry after incubation of the cell preparations with 100μM of pregnenolone and appropriate concentrations of ethanol (1–100mM). Concentrations of all 4-ene-steroids measured were significantly decreased even at the lowest concentration of ethanol. When NAD+(0.1 mM) was added to the incubation medium, the levels of progesterone and 17-hydroxyprogesterone returned to control values, whereas those of androstenedione and testosterone remained decreased. These results suggest that ethanol may inhibit testicular steroidogenesis by suppressing at least two steps in the pregnenolone-to-testosterone pathway, the pregnenolone-to-progesterone step catalysed by NAD+-dependent 5-ene-3β-hydroxysteriod dehydrogenase/isomerase and the 17-hydroxyprogesterone-to-androstenedione step catalysed by the NAD+-independent C17–20
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