EFFECTS OF FINASTERIDE AND EPRISTERIDE ON STEROID 5α-REDUCTASE KINETICS — A COMPARATIVE IN VITRO STUDY

Objective: To compare the effect of finasteride with that of epristeride on 5α-reductase kinetics in vitro to explain the increase in serum testosterone level by finasteride but not by epristeride when treated for benign prostatic hyperplasia. Methods: Sprague-Dawley rat liver microsomal crude suspension served as the source of steroid 5α-reductase. The enzyme, Tris-HCl buffer, [ 3 H] testosterone and epristeride or finasteride were incubated together at 37°C for 20 min. The substrate, [ 3 H] testosterone, and its product, [ 3 H] dihydrotestosterone (DHT) were isolated by thin-layer chromatography. To measure the initial velocity of [ 3 H] DHT (the activity of 5α-reductase), the radioactivity of [ 3 H] DHT, scrapped off thin-layer plate was determined with isotope scintillation counter. The enzyme activity was expressed as μM/min of [ 3 H] DHT. Results: Epristeride was an uncompetitive inhibitor, but finasteride was a competitive one to steroid 5α-reductase and their inhibition constants were 67±19 and 25±3 nM, respectively. Conclusion: The inhibition mechanism of finasteride different from epristeride perhaps was the reason for increase in serum testosterone levels in patients with benign prostatic hyperplasia treated by finasteride.