KINETIC-ANALYSIS OF ANDROSTENEDIONE 5-ALPHA-REDUCTASE IN EPITHELIUM AND STROMA OF HUMAN PROSTATE

In the human prostate, various androgen-metabolizing enzymes are prese nt. Among these enzymes, testosterone 5 alpha-reductase seems to be do minant. However, androstenedione is also a potential substrate of the prostatic 5 alpha-reductase. To address the question of to what extent the reduction of androstenedione to androstanedione occurs, the prese nt study describes in detail the kinetic characteristics (K-m and V-ma x) and possible age-dependent alterations of this enzymatic step in ep ithelium and stroma of the human prostate. In normal prostate (NPR), t he mean K-m (nM) and V-max (pmol/mg protein.h) were about twofold high er in stroma (K-m, 211; V-max, 130) than in epithelium (K-m, 120; V-ma x, 56), whereas in the benign prostatic hyperplasia (BPH), the mean K- m (nM; mean +/- SEM) and V-max (pmol/mg protein.h; mean +/- SEM) were about sixfold higher in stroma (K-m, 688 +/- 121; V-max, 415 +/- 73) t han in epithelium (K-m, 120 +/- 10; V-max, 73 +/- 8). In BPH, those di fferences between epithelium and stroma were highly significant (p < 0 .001). However, the efficiency ratios (V-max/K-m) of neither BPH nor N PR showed any significant differences between epithelium (NPR, 0.47; B PH, 0.62 +/- 0.06) and stroma (NPR, 0.70; BPH, 0.63 +/- 0.05). With re spect to age-related changes, only stroma showed a significant increas e of K-m (p < 0.01) and V-max (p < 0.05) with age. In summary, in both epithelium and stroma of the human prostate, a 5 alpha-reductase conv erts in measurable amounts androstenedione to androstanedione. The kin etic data were, in part, different between epithelium and stroma; the reason for this difference remains unclear. In comparison to other met abolic conversions, such as testosterone to dihydrotestosterone and an drostenedione to testosterone, it is unlikely that, in the human prost ate, the adrenal androgen androstenedione contributes significantly to the formation of testosterone and, further of dihydrotestosterone. (C ) 1997 by Elsevier Science Inc.