INCREASED RATIO OF 5-ALPHA-REDUCTASE - 3-ALPHA(BETA)-HYDROXYSTEROID DEHYDROGENASE-ACTIVITIES IN THE HYPERPLASTIC HUMAN-PROSTATE

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 5x10-4 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 ± 4.7 (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 the 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.