Weisser H, Tunn S, Debus M, Krieg M
Institute of Clinical Chemistry and Laboratory Medicine, University Clinic Bergmannsheil, Bochum, Germany.
Steroids. 1994 Nov;59(11):616-20. doi: 10.1016/0039-128x(94)90016-7.
Finasteride is a specific 5 alpha-reductase inhibitor that has been shown to reduce the size of human benign prostatic hyperplasia (BPH) by inhibiting the intraprostatic conversion of testosterone to 5 alpha-dihydrotestosterone. The aim of the present in vitro study was to describe in more detail the inhibitory effect of finasteride on 5 alpha-reductase in epithelium and stroma of human BPH. 5 alpha-Reductase activity in epithelium and stroma was inhibited dose-dependently by finasteride. The mean IC50 (50% inhibitory concentration) values, determined in the presence of various testosterone concentrations, were generally 2- to 4-fold lower in epithelium than in stroma. With finasteride concentrations greater than 5 nM, competitive inhibition of 5 alpha-reductase occurred both in epithelium and stroma. The mean inhibition constant Ki[nM +/- SEM] was 7 +/- 3 and 31 +/- 3 in epithelium and stroma, respectively. In the presence of finasteride concentrations < or = 5 nM, the epithelial 5 alpha-reductase seems to be inhibited in an uncompetitive manner, whereas such low finasteride concentrations cause either no inhibition (1-2 nM) or competitive inhibition (5 nM) in stroma. Our present study provides evidence that the inhibitory effect of finasteride on 5 alpha-reductase is much stronger in epithelium than in stroma. Therefore, it is conceivable that the global size-reduction of BPH under finasteride treatment is primarily due to the regression of BPH epithelium.
非那雄胺是一种特异性5α-还原酶抑制剂，已证实它可通过抑制前列腺内睾酮向5α-双氢睾酮的转化来缩小人类良性前列腺增生（BPH）的体积。本体外研究的目的是更详细地描述非那雄胺对人类BPH上皮和基质中5α-还原酶的抑制作用。非那雄胺对上皮和基质中的5α-还原酶活性呈剂量依赖性抑制。在不同睾酮浓度下测定的平均IC50（50%抑制浓度）值，上皮中的通常比基质中的低2至4倍。当非那雄胺浓度大于5 nM时，上皮和基质中均发生5α-还原酶的竞争性抑制。上皮和基质中的平均抑制常数Ki[nM +/- SEM]分别为7 +/- 3和31 +/- 3。在非那雄胺浓度≤5 nM时，上皮中的5α-还原酶似乎以非竞争性方式被抑制，而如此低的非那雄胺浓度在基质中要么无抑制作用（1 - 2 nM），要么产生竞争性抑制（5 nM）。我们目前的研究提供了证据，表明非那雄胺对5α-还原酶的抑制作用在上皮中比在基质中要强得多。因此，可以想象非那雄胺治疗下BPH的整体体积缩小主要是由于BPH上皮的消退。
