INCREASED RATIO OF 5α-REDUCTASE: 3α(β)-HYDROXYSTEROID DEHYDROGENASE ACTIVITIES IN THE HYPERPLASTIC HUMAN PROSTATE

Abstract

The activities of 5α-reductase and 3α(β)-hydroxysteroid dehydrogenase were assayed in homogenates of eight normal, 21 hyperplastic and four carcinomatous human prostates. Samples consisting of 300–500 μg tissue protein in Tris buffer, pH 7·0, were incubated at 37 °C for 30 min in the presence of 50 nm-[3H]androgen and an NADPH-generating system started with 5 × 10−4 m-NADP. The yield of 5α- and 3α-reduced metabolites, as established by using t.l.c. and g.l.c., gave an estimate of enzyme activity. The formation of metabolites denoting 5α-reductase activity in normal, hyperplastic and carcinomatous tissue respectively was 28·8 ± 47 (s.e.m.), 76·8 ± 8·9 and 3·5 ± 0·7 pmol 30 min−1 mg protein−1; similarly, that denoting 3α(β)-hydroxysteroid dehydrogenase activity was 69·3 ± 6·7, 46·6 ± 5·7 and 38·8 ± 22·1 pmol 30 min−1 mg protein−1. In all normal prostates 5α-reductase activity was lower than 3α(β)-hydroxysteroid dehydrogenase activity. Conversely, in 18 out of 21 hyperplastic prostates, 5α-reductase activity was higher than 3α(β)-hydroxysteroid dehydrogenase activity. The effect of the increase in 5α-reductase activity without a compensatory change in 3α(β)-hydroxysteroid dehydrogenase activity was to alter the mean ratio between 5α-reductase and 3α(β)-hydroxysteroid dehydrogenase activities from 0·47 ± 0·11 in the normal prostate to 1·84 ± 0·19 in hyperplastic tissue. It is inferred that this change may predispose the hyperplastic prostate to asymmetrical rates of androgen metabolism and thereby contribute to the abnormal accumulation of dihydrotestosterone.