Span P N, Völler M C, Smals A G, Sweep F G, Schalken J A, Feneley M R, Kirby R S
Department of Internal Medicine, University Hospital St. Radboud, Nijmegen, The Netherlands.
J Urol. 1999 Jan;161(1):332-7.
The type II 5alpha-reductase inhibitor finasteride is used in the treatment of benign prostatic hyperplasia (BPH), reducing local production of the growth promoting androgen dihydrotestosterone (DHT). The effect of prolonged treatment with this time-dependent irreversible inhibitor on the recently described prostatic type I 5alpha-reductase, however, is not clear. Therefore, we assessed the effects of 5 mg. finasteride per day for 6 months on prostatic 5alpha-reductase isozymes, and prostatic tissue composition and androgen content of patients suffering from BPH. In prostatic tissue from these patients, the type II enzymatic activity is inhibited 100-fold compared with tissues obtained from placebo treated patients. The type II immunoreactivity is up regulated 2-fold. The type I isozyme is inhibited 3-fold and potentially still contributes to DHT production. In conclusion, finasteride is a selective type II inhibitor in vivo. Further research is warranted to assess the possibly distinct roles of the 5alpha-reductase isozymes in the normal prostate, in BPH, and during finasteride treatment.
II型5α-还原酶抑制剂非那雄胺用于治疗良性前列腺增生（BPH），可减少促进生长的雄激素双氢睾酮（DHT）的局部生成。然而，这种时间依赖性不可逆抑制剂长期治疗对最近发现的前列腺I型5α-还原酶的影响尚不清楚。因此，我们评估了每天服用5毫克非那雄胺，持续6个月对BPH患者前列腺5α-还原酶同工酶、前列腺组织组成及雄激素含量的影响。在这些患者的前列腺组织中，与接受安慰剂治疗患者的组织相比，II型酶活性被抑制了100倍。II型免疫反应性上调了2倍。I型同工酶被抑制了3倍，但仍可能参与DHT的生成。总之，非那雄胺在体内是一种选择性II型抑制剂。有必要进一步研究，以评估5α-还原酶同工酶在正常前列腺、BPH及非那雄胺治疗期间可能存在的不同作用。
