Comparison of the nuclear 5 alpha-reduction of testosterone and androstenedione in human prostatic carcinoma and benign prostatic hyperplasia.
The nuclear conversion of testosterone (T) to dihydrotestosterone (DHT) and androstenedione (delta 4A) to androstanedione (5 alpha-Adione) was compared in the separated stromal and epithelial fractions of hyperplastic (n = 6) and malignant (n = 3) prostatic tissues. Assay conditions were linear with respect to time and protein concentration and were optimal for NADPH concentration. The apparent Km values for the stromal enzymes were 0.2 and 0.02 microM for hyperplasia and carcinoma, respectively, using T as substrate. The apparent Km values, using delta 4A as substrate, were 0.03 and 0.02 microM, respectively. Apparent Vmax values for the stromal formation of DHT were 16.5 +/- 5.4 and 1.97 +/- 0.45 pmol/mg protein/30 min incubation, respectively, for the hyperplastic and malignant tissues. The apparent Vmax values for the formation of 5 alpha-Adione were 2.8 +/- 1.3 and 6.5 +/- 1.2 pmol/mg/protein/30 min incubation. The apparent Km values for the epithelial enzyme, for hyperplastic and malignant tissue were 0.04 and 0.04 microM, for T, and 0.05 and 0.03 microM for delta 4A. The respective apparent Vmax values were 4.6 +/- 0.93 and 0.65 +/- 0.07 for DHT and 2.0 +/- 0.86 and 6.4 +/- 0.45 pmol/mg protein/30 min incubation for 5 alpha-Adione. delta 4A was a competitive inhibitor of T 5 alpha-reduction. These results provide further evidence that different rates of 5 alpha-reduction at least partially explain the differences in androgen levels seen in the hyperplastic and the malignant prostate.
Department of Medicine, Queen's University, Kingston, Ontario, Canada.
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Hudson
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Wherrett
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism*; D000735:Androstenedione / Q000378:metabolism*; D002458:Cell Fractionation; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008297:Male; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D011470:Prostatic Hyperplasia / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism*
D013739:Testosterone; D000735:Androstenedione; D009249:NADP; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase