Comparison of the nuclear 5α-reduction of testosterone and androstenedione in human prostatic carcinoma and benign prostatic hyperplasia

Abstract

The nuclear conversion of testosterone (T) to dihydrotestosterone (DHT) and androstenedione (Δ 4A) 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 K m values for the stromal enzymes were 0.2 and 0.02 μM for hyperplasia and carcinoma, respectively, using T as substrate. The apparent K m values, using Δ 4A as substrate, were 0.03 and 0.02 μM, respectively. Apparent V max 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 V max 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 K m 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 Δ 4A. The respective apparent V max 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. Δ 4A 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.