Effect of Aging on Kinetic Parameters of 3α(β)-Hydroxysteroid Oxidoreductases in Epithelium and Stroma of Human Normal and Hyperplastic Prostate

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Abstract
The accumulation of 5.alpha.-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 5.alpha.-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 5.alpha.-androstanediols. Thus, we determined, in the presence of NADPH/NADP+, kinetic parameters [Km and maximum velocity (Vmax)] of 3-hydroxysteroid oxidoreductases (3.alpha.-HSORred, 3.beta.-HSORred, and 3.alpha.-HSORox) 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 3.alpha.-HSORred 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 3.beta.-HSORred and 3.alpha.-HSORox were similar. Concerning 3.alpha.-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 3.beta.-HSORred and 3.alpha.-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 5.alpha.-reductase. With advancing age, the Vmax/Km decreased significantly (P < 0.001; 3 .alpha.-HSORred and 3.beta.-HSORred) or tendentiously (3.alpha.-HSORox) in epithelium, while in stroma a significant (p < 0.001; 3.alpha.-HSORred and 3.alpha.-HSORox) or tendentious (3.beta.-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 5.alpha.-reductase.