5-ALPHA-REDUCTASE INHIBITION BY FINASTERIDE (PROSCAR(R)) IN EPITHELIUM AND STROMA OF HUMAN BENIGN PROSTATIC HYPERPLASIA

Finasteride is a specific 5 alpha-reductase inhibitor that has been sh own to reduce the size of human benign prostatic hyperplasia (BPH) by inhibiting the intraprostatic conversion of testosterone to 5 alpha-di hydrotestosterone. The aim of the present in vitro study was to descri be in more detail the inhibitory effect of finasteride on 5 alpha-redu ctase in epithelium and stroma of human BPH. 5 alpha-Reductase activit y in epithelium and stroma was inhibited dose-dependently by finasteri de. 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 conce ntrations greater than, 5 nM, competitive inhibition of 5 alpha-reduct ase occurred both in epithelium and stroma. The mean inhibition consta nt K-i[nM +/- SEM] was 7 +/- 3 and 31 +/- 3 in epithelium and stroma, respectively In the presence of finasteride concentrations less than o r equal to 5 nM, the epithelial 5 alpha-reductase seems to be inhibite d in an uncompetitive manner, whereas such low finasteride concentrati ons cause either no inhibition (1-2 nM) or competitive inhibition (5 n M) in stroma. Our present slurry provides evidence that the inhibitory effect of finasteride on 5 alpha-reductase is much stronger in epithe lium than in stroma. Therefore, it is conceivable that the global size -reduction of BPH under finasteride treatment is primarily die to the regression of BPH epithelium.