Krieg M, Weisser H, Tunn S
Institute of Clinical Chemistry, University Clinic Bergmannsheil, Bochum, Germany.
J Steroid Biochem Mol Biol. 1995 Jun;53(1-6):395-400. doi: 10.1016/0960-0760(95)00085-e.
The entire androgen metabolism of the human prostate is an integral part of the DHT mediated cellular processes, which eventually give rise to the androgen responsiveness of the prostate. Therefore, the potential activities of various androgen metabolizing enzymes were studied. Moreover, the impact of aging on the androgen metabolism and the inhibition of 5 alpha-reductase by finasteride were studied. In epithelium (E) and stroma (S) of normal (NPR) and hyperplastic human prostate (BPH), for each enzyme being involved in the conversion either of testosterone via DHT, 3 alpha- and 3 beta-diol to the C19O3-triols or from testosterone to androstenedione and vice versa, the amount (Vmax) and Michaelis constant (Km) were determined by Lineweaver-Burk plots. Furthermore, Vmax/Km quotients were calculated, which served as an index for the potential enzyme activity. 17 enzymes showed a mean Vmax/Km > or = 0.10. The top four were the 5 alpha-reductases in E and S of NPR and BPH. Among those, the highest activity was found in E of NPR (1.6 +/- 0.2). Moreover, in E a significant age-dependent decrease of 5 alpha-reductase activity occurred, whereas in stroma rather constant activities were found over the whole age range. Similar age-dependent alterations were found for the cellular DHT levels. Finally, the finasteride inhibition of 5 alpha-reductase (IC50;nM) was stronger in E (35 +/- 17) than in S (126 +/- 15). In conclusion, 5 alpha-reductase is: (a) the outstanding androgen metabolizing enzyme in NPR and BPH; (b) dictating the DHT enrichment in the prostate; (c) under the impact of aging; and (d) preferentially inhibited by finasteride in E.
人类前列腺的整个雄激素代谢是双氢睾酮（DHT）介导的细胞过程的一个组成部分，最终导致前列腺对雄激素产生反应。因此，对各种雄激素代谢酶的潜在活性进行了研究。此外，还研究了衰老对雄激素代谢的影响以及非那雄胺对5α-还原酶的抑制作用。在正常（NPR）和增生性人类前列腺（BPH）的上皮（E）和基质（S）中，对于参与睾酮经DHT、3α-和3β-二醇转化为C19O3-三醇，或从睾酮转化为雄烯二酮及反之的每种酶，通过Lineweaver-Burk图测定其含量（Vmax）和米氏常数（Km）。此外，计算了Vmax/Km商数，其作为潜在酶活性的指标。17种酶的平均Vmax/Km≥0.10。排名前四位的是NPR和BPH的E和S中的5α-还原酶。其中，NPR的E中活性最高（1.6±0.2）。此外，在E中5α-还原酶活性出现显著的年龄依赖性下降，而在基质中，在整个年龄范围内活性相当恒定。细胞DHT水平也发现了类似的年龄依赖性变化。最后，非那雄胺对5α-还原酶的抑制作用（IC50；nM）在E中（35±17）比在S中（126±15）更强。总之，5α-还原酶是：（a）NPR和BPH中杰出的雄激素代谢酶；（b）决定前列腺中DHT的富集；（c）受衰老影响；（d）在E中优先被非那雄胺抑制。
