EFFECT OF AGING ON KINETIC-PARAMETERS OF 3-ALPHA(BETA)-HYDROXYSTEROID OXIDOREDUCTASES IN EPITHELIUM AND STROMA OF HUMAN NORMAL AND HYPERPLASTIC PROSTATE

The accumulation of 5α-dihydrotestosterone (DHT), particularly in stroma, is a possible etiological factor in regard of the age-dependent development of benign prostatic hyperplasia (BPH). In this context, we have recently demonstrated age-dependent alterations of 5α-reductase, which is responsible for the irreversible conversion of testosterone to DHT. Therefore, it was also of interest to study possible age-dependent alterations of those enzymes mainly involved in the reversible metabolism of DHT to 5α-androstanediols. Thus, we determined, in the presence of NADPH/NADP+, kinetic parameters [Km and maximum velocity (Vmax)] of 3-hydroxysteroid oxidoreductases (3α-HS0Rred, 3β-HSORred, and 3α-HS0Rox) in separated epithelium and stroma of 10 normal (NPR) and 20 hyperplastic prostates (BPH) and correlated the data with the age of the donors (15–86 yr). The mean Km (nanomolar concentrations ± SEM) of 3α-HS0Rred was significantly (P < 0.01) higher in epithelium (NPR, 1391 ± 181; BPH, 2150 ± 157) than in stroma (NPR, 778 ± 22; BPH, 749 ± 62), indicating the presence of epithelial and stromal enzymes. The mean Km values of 3β-HSORred and 3α-HSORox were similar. Concerning 3α-HSORred, the mean potential capacity, i.e. the quotient of Vmax/ Km (±SEM), was significantly (P < 0.01) higher in epithelium (0.56 ± 0.08) than in stroma (0.19 ± 0.02) of NPR, while in BPH nearly identical mean potential capacities were found in epithelium (0.33 ± 0.04) and stroma (0.26 ± 0.02). The respective Vmax/Km of S/S-HSORred and 3α-HSORox were significantly (P < 0.05) lower. In addition, the potential capacity of all three enzymes was distinctly lower than the potential DHT-forming capacity of 5α-reductase. With advancing age, the Vmax/Km decreased significantly (P < 0.001; 3α-HS0Rred and 3β-HSORred) or tendentiously (3α-HSORox) in epithelium, while in stroma a significant (P < 0.001; 3α-HSORred and 3α-HSORox) or tendentious (3β-HSORred) increase with age was found. Our results indicate that aging has a significant impact on DHT-removing enzymes. However, these enzymes counterbalance only in part the strong potential capacity of 5α-reductase. © 1990 by The Endocrine Society.