Testosterone metabolism by homogenates of human prostates with benign hyperplasia: effects of zinc, cadmium and other bivalent cations.
The effects of various quantities of Ba, Be, Ca, Cd, Co, Cu, Mg, Mn, Sr, Zn and EDTA on the formation of 5 alpha-reduced metabolites of testosterone (T) substrate and of 3 alpha-/3 beta-reduced metabolites of 5 alpha-dihydrotestosterone substrates by homogenates of 6 human hyperplastic prostate glands were studied in incubations at pH 7.4 with NADPH-generating system. Effects of these cations and EDTA on the VM and KM of the 5 alpha-reductase and 3 alpha-/3 beta-hydroxysteroid dehydrogenases (-HSD) were also measured. Quantities of 5 alpha-reduced T metabolites were significantly increased by Cd, Cu and Zn supplementations. These increments were shown to result from significant augmentations of the VM but no change in KM of the NADPH-dependent 5 alpha-reductase. Quantities of 3 alpha-reduced DHT metabolites were significantly decreased by Cd and Cu supplementations and resulted from an increase of the KM of the NADPH-dependent 3 alpha-HSD by Cd and both an increase of KM and a decrease of VM by Cu. Quantities of 3 beta-reduced DHT metabolites were significantly decreased by Cd and Cu supplementations. Increase of the KM of the NADPH-dependent 3 beta-HSD by Cd was found significant while Cu both increased the KM and decreased the VM of the enzyme. EDTA-related changes in 5 alpha-reductase activity were shown to result from the EDTA-induced decrease of the pH of the medium. No effect of EDTA was observed on the activities of both 3 alpha/3 beta-HSD.
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D002104:Cadmium / Q000494:pharmacology*; D002250:Carbon Radioisotopes; D002413:Cations, Divalent; D013196:Dihydrotestosterone / Q000378:metabolism; D004492:Edetic Acid / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008297:Male; D011467:Prostate / Q000187:drug effects / Q000378:metabolism*; D011470:Prostatic Hyperplasia / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism*; D015032:Zinc / Q000494:pharmacology*
D002250:Carbon Radioisotopes; D002413:Cations, Divalent; D002104:Cadmium; D013196:Dihydrotestosterone; D013739:Testosterone; D004492:Edetic Acid; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D015032:Zinc