Kinetic analysis of androstenedione 5 alpha-reductase in epithelium and stroma of human prostate.
In the human prostate, various androgen-metabolizing enzymes are present. Among these enzymes, testosterone 5 alpha-reductase seems to be dominant. 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 present study describes in detail the kinetic characteristics (Km and Vmax) and possible age-dependent alterations of this enzymatic step in epithelium and stroma of the human prostate. In normal prostate (NPR), the mean Km (nM) and Vmax (pmol/mg protein.h) were about twofold higher in stroma (Km, 211; Vmax, 130) than in epithelium (Km, 120; Vmax, 56), whereas in the benign prostatic hyperplasia (BPH), the mean Km (nM; mean +/- SEM) and Vmax (pmol/mg protein.h; mean +/- SEM) were about sixfold higher in stroma (Km, 668 +/- 121; Vmax, 415 +/- 73) than in epithelium (Km, 120 +/- 10; Vmax, 73 +/- 8). In BPH, those differences between epithelium and stroma were highly significant (p < 0.001). However, the efficiency ratios (Vmax/Km) of neither BPH nor NPR showed any significant differences between epithelium (NPR, 0.47; BPH, 0.62 +/- 0.06) and stroma (NPR, 0.70; BPH, 0.63 +/- 0.05). With respect to age-related changes, only stroma showed a significant increase of Km (p < 0.01) and Vmax (p < 0.05) with age. In summary, in both epithelium and stroma of the human prostate, a 5 alpha-reductase converts in measurable amounts androstenedione to androstanedione. The kinetic data were, in part, different between epithelium and stroma; the reason for this difference remains unclear. In comparison to other metabolic conversions, such as testosterone to dihydrotestosterone and androstenedione to testosterone, it is unlikely that, in the human prostate, the adrenal androgen androstenedione contributes significantly to the formation of testosterone and, further, of dihydrotestosterone.
Weisser
H
H
Institute of Clinical Chemistry, University Clinic Bergmannsheil, Bochum, Germany.
Krieg
M
M
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000735:Androstenedione / Q000378:metabolism*; D004848:Epithelium / Q000201:enzymology; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009249:NADP / Q000494:pharmacology; D011467:Prostate / Q000201:enzymology*; D011470:Prostatic Hyperplasia / Q000201:enzymology; D017154:Stromal Cells / Q000201:enzymology
D000735:Androstenedione; D009249:NADP; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase