Distinct Testicular 17xetosteroid Reductases, One in Inte~~ti~ Tissue and One in Se~~iferous Tub~es Differential Modulation by Testosterone and Metabolites of Testosterone

The final step in the biosynthesis of testosterone is the reduction of androstenedione, which is catalyzed by the microsomal enzyme 17-ketosteroid reductase. Evidence is presented which suggests that there are two distinct 17ketosteroid reductases in rat testes, one in interstitial tissue and one in seminiferous tubules. The two enzymes have different pH optima, 5.6 for the one from interstitial tissue and 6.5 for the one from seminiferous tubules. At the optimum pH, a 70-fold difference in K, values was observed, 17 tiM for the interstitial tissue enzyme and 0.25 PM for the enzyme from seminiferous tubules. Testosterone and me~boli~s of testosterone have very different effects on each of these enzyme activities. The interstitial tissue enzyme activity is inhibited by testosterone and several &reduced metabolites of testosterone and by estrogens. The most potent inhibitor of the steroids investigated was 5aandrostane-3ol ,l’Ipdiol, followed by l’lfi-estradiol s dihydrotestosterone > testosterone > estrone > estriol. 5~-~drost~e-3~,~7~~iol and 17&estradiol were shown to a&t by competitive ~hibition with apparent I& values of 2.2 and 3.7 PM, respectively. In contrast, it was demonstrated that among the above steroids, only dihydrotestosterone inhibits the 17-ketosteroid reductase activity of seminiferous tubules and this inhibition was only observed at very high concentrations of inhibitor. Testosterone stimulated the 17-ketosteroid reductase activity of seminiferous tubules. 5~-Androst~e-3~,17~diol at low concentrations stim-