Inhibition of androgen metabolism in stroma and epithelium of the human benign prostatic hyperplasia by progesterone, estrone, and estradiol.
It has been shown that progesterone, estrone, and estradiol are present in significant amounts in the human benign prostatic hyperplasia (BPH). Therefore it was of interest to determine the inhibitory effect of these steroids on the 5 alpha-reductase and 3 alpha (beta)-hydroxysteroiddehydrogenase (HSDH) activities, the enzymes responsible for the conversion of testosterone to 5 alpha-dihydrotestosterone (DHT), and DHT to 3 alpha (beta)-androstanediols, respectively. The enzyme inhibition was analyzed in vitro by measuring the 5 alpha-reductase in the presence of either progesterone, estrone, or estradiol, using testosterone as substrate. The DHT was used as substrate for HSDH. The metabolites were quantified by t.l.c. The main results were as follows: (1) Concerning 5 alpha-reductase in BPH, the mean inhibitor constants (KI; microM) of progesterone, estrone, and estradiol were 0.11, 15.5, and 5.1, respectively. (2) Analyzing epithelium and stroma of BPH separately, the inhibition of 5 alpha-reductase resulted in nearly identical KI's. (3) Concerning HSDH in BPH, the mean KI's of progesterone, estrone, and estradiol were 169, 63, and 192, respectively. (4) Analyzing epithelium and stroma of BPH separately, the inhibition of HSDH led to nearly identical KI's. (5) The kinetic parameters (KM, Vmax) of the 5 alpha-reduction of progesterone and testosterone were nearly identical. These results led to the suggestion that the endogenous concentrations of progesterone, estrone, and estradiol have no significant inhibitory effect on the 5 alpha-reductase and HSDH in vivo. Furthermore, the nearly identical inhibitor constants found for both enzymes in epithelium and stroma of BPH indicate that in both compartments the 5 alpha-reductase and HSDH are qualitatively identical.
Krieg
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Schlenker
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D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D058891:5-alpha Reductase Inhibitors; D004848:Epithelium / Q000201:enzymology; D004958:Estradiol / Q000494:pharmacology*; D004970:Estrone / Q000494:pharmacology*; D006801:Humans; D006915:Hydroxytestosterones / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D011374:Progesterone / Q000494:pharmacology*; D011467:Prostate / Q000187:drug effects / Q000201:enzymology*; D011470:Prostatic Hyperplasia / Q000201:enzymology*; D013739:Testosterone / Q000378:metabolism
D058891:5-alpha Reductase Inhibitors; D006915:Hydroxytestosterones; D004970:Estrone; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D015096:3-Hydroxysteroid Dehydrogenases