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.