Increased ratio of 5 alpha-reductase: 3 alpha (beta)-hydroxysteroid dehydrogenase activities in the hyperplastic...

The activities of 5 alpha-reductase and 3 alpha (beta)-hydroxysteroid dehydrogenase were assayed in homogenates of eight normal, 21 hyperplastic and four carcinomatous human prostates. Samples consisting of 300--500 microgram tissue protein in Tris buffer, pH 7.0, were incubated at 37 degrees C for 30 min in the presence of 50 nM-[3H]androgen and an NADPH-generating system started with 5 X 10(-4)M-NADP. The yield of 5 alpha- and 3 alpha-reduced metabolites, as established by using t.l.c. and g.l.c., gave an estimate of enzyme activity. The formation of metabolites denoting 5 alpha-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 3 alpha (beta)-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 5 alpha-reductase activity was lower than 3 alpha (beta)-hydroxysteroid dehydrogenase activity. Conversely, in 18 out of 21 hyperplastic prostates, 5 alpha-reductase activity was higher than 3 alpha (beta)-hydroxysteroid dehydrogenase activity. The effect of the increase in 5 alpha-reductase activity without a compensatory change in 3 alpha (beta)-hydroxysteroid dehydrogenase activity was to alter the mean ratio between 5 alpha-reductase and 3 alpha (beta)-hydroxysteriod 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.