COMPARISON OF THE NUCLEAR 5-ALPHA-REDUCTION OF TESTOSTERONE AND ANDROSTENEDIONE IN HUMAN PROSTATIC-CARCINOMA AND BENIGN PROSTATIC HYPERPLASIA

The nuclear conversion of testosterone (T) to dihydrotestosterone (DHT) and androstenedione (Δ4A) to androstanedione (5α-Adione) was compared in the separated stromal and epithelial fractions of hyperplastic (n = 6) and malignant (n = 3) prostatic tissues. Assay conditions were linear with respect to time and protein concentration and were optimal for NADPH concentration. The apparent Km values for the stromal enzymes were 0.2 and 0.02 μM for hyperplasia and carcinoma, respectively, using T as substrate. The apparent Km values, using Δ4A as substrate, were 0.03 and 0.02 μM, respectively. Apparent Vmax values for the stromal formation of DHT were 16.5 ± 5.4 and 1.97 ±0.45 pmol/mg protein/30min incubation, respectively, for the hyperplastic and malignant tissues. The apparent Vmax values for the formation of 5α-Adione were 2.8 ± 1.3 and 6.5 ± 1.2 pmol/mg/protein/30 min incubation. The apparent Km values for the epithelial enzyme, for hyperplastic and malignant tissue were 0.04 and 0.04 μM, for T, and 0.05 and 0.03 μM for Δ4A. The respective apparent Vmax values were 4.6 ±0.93 and 0.65 ±0.07 for DHT and 2.0 ±0.86 and 6.4 ± 0.45 pmol/mg protein/30 min incubation for 5α-Adione. Δ4A was a competitive inhibitor of T 5α-reduction. These results provide further evidence that different rates of 5α-reduction at least partially explain the differences in androgen levels seen in the hyperplastic and the malignant prostate. © 1990.