METABOLISM OF DEHYDROEPIANDROSTERONE BY RAT TESTICULAR HOMOGENATES; KINETIC STUDY AT DIFFERENT TEMPERATURES; DIRECT EFFECT OF 17 -OESTRADIOL

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[4-14C] Dehydroepiandrosterone was incubated with rat testicular homogenates at 37°C and at 4°C. At 37°C the formation of radioactive androst-4-ene-3,17-dione reached its maximum after incubation for 30 min, and testosterone after 60 min. A third metabolite consisting of a radioactive compound tentatively identified as androst-5-ene-3,17-diol was found in minute quantities. When the substrate was incubated in the presence of NADP it was rapidly converted to androst-4-ene-3,17-dione (maximum after 10 min of incubation) and was followed by an accelerated formation of testosterone. Following incubation at 4°C, androst-4-ene-3,17-dione was found to be the main metabolite, being formed up to 60 min in equal amounts as at 37°C. The formation of testosterone, however, was clearly reduced throughout the incubation period. Androst-5-ene-3,17-diol was found in small amounts. The addition of NADP to the incubation medium accelerated the formation of androst-4-ene-3,17-dione but had no effect on the formation of testosterone. 17β-Oestradiol added in a concentration of 6.1 × 10−6 mol/l inhibited the formation of testosterone after incubation for one hour at 37°C. At higher concentrations (6.1 × 10−5 mol/l–6.1 × 10−4 mol/l) the recovery of androst-4-ene-3,17-dione was also reduced. The mechanism involved in the inhibitory action of 17β-oestradiol on testosterone formation is discussed.

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