IN-VITRO INHIBITION OF ANDROSTENEDIONE 5-ALPHA-REDUCTION BY FINASTERIDE IN EPITHELIUM AND STROMA OF HUMAN BENIGN PROSTATIC HYPERPLASIA

Finasteride is a well known steroid 5 alpha-reductase inhibitor. In th is context, recently we have shown that in human benign prostatic hype rplasia (BPH) finasteride inhibits the 5 alpha-reduction of testostero ne to dihydrostestosterone (DHT) more effectively in the epithelium as compared to the stroma. The aim of the present study was to describe in epithelium and stroma of human BPH the effect of finasteride on the Set-reduction of androstenedione, that is the second main circulating androgen in men, to androstanedione. Using a finasteride concentratio n of 75 nlM and an androstenedione concentration of 220 nM, the mean i nhibition [%+/-SEM] of 5 alpha-reductase activity was significantly hi gher in epithelium (69 +/- 2) than in stroma (52 +/- 4). Both in epith elium and stroma, this inhibition of 5 alpha-reductase activity was do se-dependent and competitive. Dixon plots as well as slope replots of Lineweaver-Burk plots showed that the mean inhibition constant K-i (nM +/- SEM) was significantly lower in epithelium (10 +/- 1 and 11 +/- 2 , respectively) than in stroma (33 +/- 7 and 28 +/- 4, respectively) i ndicating a significantly stronger inhibitory effect of finasteride in epithelium. From those mean K-i values, it follows that in human BPH finasteride inhibits equally well both the 5 alpha-reduction of andros tenedione to androstanedione and testosterone to DHT. Based on these i nhibition studies, there is no evidence for the coexistence of substra te-specific 5 alpha-reductases converting either testosterone or andro stenedione. However, the striking difference in finasteride sensitivit y of the 5 alpha-reduction between epithelium and stroma could be due to a cell-type specific expression of structurally different 5 alpha-r eductases as well as to a different access of finasteride to 5 alpha-r eductase in epithelium and stroma where, compared to each other, the l ipid environment is significantly different. (C) 1998 Elsevier Science Ltd. All rights reserved.