The effect of zinc on the 5 alpha-reduction of testosterone by the hyperplastic human prostate gland.

The present studies were performed to evaluate the role of zinc in the regulation of testosterone 5 alpha-reduction by the 800 g supernatants prepared from human benign prostate hyperplasia specimens. The results show that when zinc is added at low concentrations the 5 alpha-reduction of testosterone is increased but at higher cation concentrations the metabolism is significantly inhibited. This decrease was mediated by both a non-competitive inhibition of the binding of testosterone to the 5 alpha-reductase enzyme and by a reduction in the formation of the NADPH cofactor. We have also demonstrated that the decreased synthesis of NADPH was produced by a competitive inhibition of both G6P and NADP binding to the G6PD enzyme. The data also suggests that the increase in testosterone metabolism observed at low zinc concentrations does not produce any changes in the binding of testosterone to the 5 alpha-reductase enzyme. In spite of the above observations we were unable to establish any correlation between the endogenous zinc content of the tissue and the in vitro capacity of the BPH samples to 5 alpha-reduce testosterone. The present study suggests a possible physiological role for the regulation of testosterone metabolism by zinc in the human prostate gland.