Zinc Concentration and Progestin Receptor in Human Benign Hyperplastic Prostate

Abstract

The effect of cationic zinc on the specific binding of the synthetic progestin, promegestone (17α-21-dimethyl-19-nor-pregna-4,9-diene-3,20-dione, R5020), has been investigated in cytosols from human benign hyperplastic prostate. Zinc was analyzed using flameless atomic absorption spectrometry. Progestin specific binding was assayed using sucrose density gradient centrifugation in a vertical tube rotor. The concentration of endogenous zinc in benign hyperplastic prostate cytosols was 0.53mM ± 0.26 (range 0.15mM to 0.88mM). No significant relationship was observed between zinc concentration in cytosols and the amount of progestin specific binding in the 7-8S peak in sucrose density gradients. Addition of excess zinc to cytosols (1.6mM) in the presence or absence of monothioglycerol had no effect on the total amount of 7-8S progestin specific binding observed. Removal of free zinc by gel filtration of cytosols on Sephadex G-25 did not change the amount of 7-8S cytosolic receptor binding observed. The addition of the chelating agents, 2,2’,2"-tripyridine, 9,10-phenanthroline or EGTA, after the gel filtration step had no apparent effect on the 7-8S progestin specific binding. The anionic chelator, EDTA, inhibited the 7-8S specific binding in a dose dependent manner. However, this inhibition was not reversed by the addition of excess zinc (6mM) and was observed at very high concentrations of EDTA. This suggests that the effect of EDTA was due to its anionic effect rather than to its effect as a chelator. We conclude that cationic zinc in concentrations up to 2mM does not change the amount of 7-8S progestin specific receptor binding in cytosols from BPH tissue.