5 alpha-reductase inhibition by finasteride (Proscar) in epithelium and stroma of human benign prostatic hyperplasia.
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.
Weisser
H
H
Institute of Clinical Chemistry and Laboratory Medicine, University Clinic Bergmannsheil, Bochum, Germany.
Tunn
S
S
Debus
M
M
Krieg
M
M
D058891:5-alpha Reductase Inhibitors; D000368:Aged; D000369:Aged, 80 and over; D004848:Epithelium / Q000187:drug effects / Q000201:enzymology; D018120:Finasteride / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011470:Prostatic Hyperplasia / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D017154:Stromal Cells / Q000187:drug effects / Q000201:enzymology
D058891:5-alpha Reductase Inhibitors; D018120:Finasteride