INCREASED RATIO OF 5\g=a\-REDUCTASE: 3\g=a\(\g=b\)-HYDROXYSTEROID DEHYDROGENASE ACTIVITIES IN THE HYPERPLASTIC HUMAN

The activities of 5\g=a\-reductase and 3\g=a\(\g=b\)-hydroxysteroiddehydrogenase were assayed in homogenates of eight normal, 21 hyperplastic and four carcinomatous human prostates. Samples consisting of 300\p=n-\500 \g=m\gtissue protein in Tris buffer, pH 7\m=.\0,were incubated at 37 \s=deg\Cfor 30 min in the presence of 50 nm-[3H]androgen and an NADPH-generating system started with 5 \m=x\10\m=-\4m-NADP. The yield of 5\g=a\- and 3\g=a\-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\g=a\-reductase activity in normal, hyperplastic and carcinomatous tissue respectively was 28\m=.\8\m=+-\47(s.e.m.), 76\m=.\8\m=+-\8\m=.\9and 3\m=.\5\m=+-\0\m=.\7pmol 30 min\m=-\1mg protein\m=-\1; similarly, that denoting 3\g=a\(\g=b\)-hydroxysteroiddehydrogenase activity was 69\m=.\3\m=+-\6\m=.\7,46\m=.\6\m=+-\5\m=.\7and 38\m=.\8 \m=+-\ 22\m=.\1pmol 30 min\m=-\1mg protein\m=-\1. In all normal prostates 5\g=a\-reductase activity was lower than 3\g=a\(\g=b\)-hydroxysteroiddehydrogenase activity. Conversely, in 18 out of 21 hyperplastic prostates, 5\g=a\-reductase activity was higher than 3\g=a\(\g=b\)-hydroxysteroiddehydrogenase activity. The effect of the increase in 5\g=a\-reductase activity without a compensatory change in 3\g=a\(\g=b\)-hydroxysteroiddehydrogenase activity was to alter the mean ratio between 5\g=a\\x=req-\ reductase and 3\g=a\(\g=b\)-hydroxysteroiddehydrogenase activities from 0\m=.\47\m=+-\0\m=.\11in the normal prostate to 1\m=.\84\m=+-\0\m=.\19in 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