POTENTIAL ACTIVITIES OF ANDROGEN METABOLIZING ENZYMES IN HUMAN PROSTATE

The entire androgen metabolism of the human prostate is an integral pa rt of the DHT mediated cellular processes, which eventually give rise to the androgen responsiveness of the prostate. Therefore, the potenti al activities of various androgen metabolizing enzymes were studied. M oreover, the impact of aging on the androgen metabolism and the inhibi tion of 5 alpha-reductase by finasteride were studied. In epithelium ( E) and stroma (S) of normal (NPR) and hyperplastic human prostate (BPH ), for each enzyme being involved in the conversion either of testoste rone via DHT, 3 alpha- and 3 beta-diol to the C19O3-triols or from tes tosterone to androstenedione and vice versa, the amount (V-max) and Mi chaelis constant (K-m) were determined by Lineweaver-Burk plots. Furth ermore, V-max/K-m quotients were calculated, which served as an index for the potential enzyme activity. 17 enzymes showed a mean V-max/K-m greater than or equal to 0.10. The top four were the 5 alpha-reductase s in E and S of NPR and BPH. Among those, the highest activity was fou nd in E of NPR (1.6 +/- 0.2). Moreover, in E a significant age-depende nt decrease of 5 alpha-reductase activity occurred, whereas in stroma rather constant activities were found over the whole age range. Simila r age-dependent alterations were found for the cellular DHT levels. Fi nally, the finasteride inhibition of 5 alpha-reductase (IC50;nM) was s tronger in E (35 +/- 17) than in S (126 +/- 15). In conclusion, 5 alph a-reductase is: (a) the outstanding androgen metabolizing enzyme in NP R and BPH; (b) dictating the DHT enrichment in the prostate; (c) under the impact of aging; and (d) preferentially inhibited by finasteride in E.