5α-Reductase inhibition by finasteride (proscar®) in epithelium and stroma of human benign prostatic hyperplasia
1994; Elsevier BV; Volume: 59; Issue: 11 Linguagem: Inglês
10.1016/0039-128x(94)90016-7
ISSN1878-5867
AutoresHeike Weißer, Sabine Tunn, M. Debus, Michael Krieg,
Tópico(s)Aldose Reductase and Taurine
ResumoFinasteride is a specific 5α-reductase inhibitor that has been shown to reduce the size of human benign prostatic hyperplasia (BHP) by inhibiting the intraprostatic conversion of testosterone to 5α-dihydrotestosterone. The aim of the present in vitro study was to describe in more detail the inhibitory effect of finasteride on 5α-reductase in epithelium and stroma of human BPH. 5α-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 the 5 nM, competitive inhibition of 5α-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 ≤5 nM, the epithelial 5α-reductase seems to be inhibited in an umcompetitive manner, whereas such low finasteride concentrations cause either no inhibition (1–2 nM) or competitive inhibition (5 nM) in stroma. Our present study provides evidenmce that the inhibitory effect of finasteride on 5α-reductase is much stronger in epithelium than in stroma. Therefore, it is conceivable that the global size-reduction of BPH under finasteride treatment due to the regression of BPH epithelium.
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