Studies of the nuclear 5α-reductase of human prostatic tissue: comparison of enzyme activites in hyperplastic, malignant, and normal tissues

Abstract

The nuclear conversion of testosterone (T) to dihydrotestosterone (DHT) was compared in hyperplastic (n = 40), malignant (n = 20), and normal (n = 3) prostatic tissues. Standard assay conditions were 2 μM testosterone, 2.0 mM EDTA, 1.0 mM NADPH, and the nuclear fraction equivalent to 200 mg of prostatic tissue, in 0.1 M N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid buffer (pH 7.4). The Km values were 0.6, 0.5, and 0.3 μM, respectively, for the enzymes in hyperplastic, malignant, and normal tissues. The Vmax values were 42 ± 17, 4.2 ± 1.8, and 3.9 ± 0.9 pmol/mg protein per 30 min of incubation, respectively, for the hyperplastic, malignant, and normal tissues. When DHT formation was measured at T concentrations equivalent to reported endogenous levels, it was found that enzyme activity in the hyperplastic tissue was still greater than that in the other two tissues. The enzyme in the malignant prostate was less efficient than the enzyme in normal tissue in converting T to DHT. These results would suggest that differences in the conversion of T to DHT may explain, at least in part, the higher DHT levels seen in hyperplastic tissue than in either the normal or the malignant prostate and the higher T levels seen in the malignant prostate than in the other two tissues.