Murono E P, Payne A H
Biochim Biophys Acta. 1976 Oct 21;450(1):89-100. doi: 10.1016/0005-2760(76)90301-5.
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 17-ketosteroid 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 Km values was observed, 17 muM for the interstitial tissue enzyme and 0.25 muM for the enzyme from seminiferous tubules. Testosterone and metabolites of testosterone have very different effects of each of these enzyme activities. The interstitial tissue enzyme activity is inhibited by testosterone and several 5alpha-reduced metabolites of testosterone and by estrogens. The most potent inhibitor of the steroids investigated was 5alpha-androstane-3alpha, 17beta-diol, followed by 17beta-estradiol approximately equal to dihydrotestosterone greater than testosterone greater than estrone greater than estriol. 5alpha-Androstane-3alpha, 17beta-diol and 17beta-estradiol were shown to act by competitive inhibition with apparent Ki values of 2.2 and 3.7 muM, 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. 5alpha-Androstane-3alpha, 17beta-diol at low concentrations stimulated the enzyme activity from seminiferous tubules, while it had no effect at high concentrations. The remainder of the steroids tested had no effect on the 17-ketosteroid reductase activity of seminiferous tubules. The difference in response of the two enzyme activities suggests a mechanism for local regulation of testosterone synthesis in each testicular compartment that does not involve directly pituitary gonadotropins.
睾酮生物合成的最后一步是雄烯二酮的还原，这一过程由微粒体酶17 - 酮类固醇还原酶催化。有证据表明，大鼠睾丸中存在两种不同的17 - 酮类固醇还原酶，一种存在于间质组织，另一种存在于生精小管。这两种酶具有不同的最适pH值，间质组织中的酶最适pH值为5.6，生精小管中的酶最适pH值为6.5。在最适pH值下，观察到Km值有70倍的差异，间质组织酶的Km值为17μM，生精小管酶的Km值为0.25μM。睾酮及其代谢产物对这两种酶的活性有非常不同的影响。间质组织酶的活性受到睾酮及其几种5α - 还原代谢产物以及雌激素的抑制。在所研究的类固醇中，最有效的抑制剂是5α - 雄烷 - 3α,17β - 二醇，其次是17β - 雌二醇，其抑制作用大致等同于二氢睾酮，大于睾酮，大于雌酮，大于雌三醇。5α - 雄烷 - 3α,17β - 二醇和17β - 雌二醇表现为竞争性抑制作用，其表观Ki值分别为2.2和3.7μM。相反，已证明在上述类固醇中，只有二氢睾酮抑制生精小管的17 - 酮类固醇还原酶活性，并且这种抑制作用仅在非常高的抑制剂浓度下才观察到。睾酮刺激生精小管的17 - 酮类固醇还原酶活性。低浓度的5α - 雄烷 - 3α,17β - 二醇刺激生精小管的酶活性，而高浓度时则无作用。所测试的其余类固醇对生精小管的17 - 酮类固醇还原酶活性无影响。这两种酶活性反应的差异提示了一种在每个睾丸区室中局部调节睾酮合成的机制，该机制不直接涉及垂体促性腺激素。
