Androgen Metabolism Effects of 4-Hydroxyandrostenedione and Other Inhibitors on Lack of Evidence for Aromatase in Human Prostatic Tissues: Updated Version

The effects of 4-hydroxyandrostenedione (4-OHA) and other aromatase inhibitors, 10-propargylestr-4-ene-3,17-dione and imidazo|l,5-a|3,4,5,6-tetrahydropyrin-6-yl-(4-benzonitrile), as well as 5a-reductase in hibitors /V./V-diethyW-methyl-S-oxo^-aza-Sa-androstane-n/J-carboxyamide and 4-methyl-3-oxo-4-aza-androsta-5-ene-17-ol were investigated in prostatic tissue from six patients with benign prostatic hypertrophy and seven patients with prostatic cancer, and from normal men at autopsy. We attempted to measure aromatase activity in the tissue incubations by quantitating 'IM) released from androstenedione or testosterone labeled at the C-l position. High performance liquid Chromatograph} and thin layer chromatography were used to isolate steroid products. Although the amount of 3H2Oreleased was at least twice that of the heat-inactivated tissue samples, no estrone or estradiol was detected on high performance liquid chromatography. The 'I !..() release was significantly inhibited by 4-OHA and jV,/V-diethyl-4-metnyl-3-oxo-4-aza-5a-androstane-17/3-carboxyamide, but not by the other aromatase inhibitors. 4-OHA also inhibited 5or-reductase in both benign prostatic hypertrophy and cancer tissue, although to a lesser extent than A'tA'-diethyl-4-methyl-3-oxo-4aza-5a-androstane-17/3-carboxyamide. The other aromatase inhibitors were without effect on 5a-reductase. Our results indicate that 'IM) released from [l/3-'H]androstenedione and [l,2,6,7-3H]androstenedione does not correlate with estrogen formation and may be the result of other metabolic reactions. Although it appears that the prostate lacks aroma tase, 4-OHA may be of benefit in patients with benign prostatic hyper trophy or prostatic cancer by inhibiting this enzyme in peripheral tissue.