Inhibition of androgen-receptor interaction in mouse prostate gland cytosol by divalent metal ions
Donovan, M.P.; Schein, L.G.; Thomas, J.A.
Molecular Pharmacology 17(2): 156-162
1980
ISSN/ISBN: 0026-895X PMID: 7393202 Document Number: 162935
The binding of [3H]dihydrotestosterone to receptor proteins was studied in cytoplasm of mouse anterior prostate gland. K+, Ca2+, Mn2+, Mg2+ and Ni2+ had little effect on binding at concentrations up to 10-3 M (0.2 m K+). Pb2+, Fe2+ and Co2+ produced substantial inhibition of binding at 10-3 M. Cu2+, Hg2+, Zn2+ and Cd2+ were very effective inhibitors producing 50% inhibition at 2-3 .times. 10-5 M and nearly 100% inhibition at 10-4 M. The inhibition due to Zn2+ was competitive. These observations are consistent with the possible involvement of Zn2+ in negative feedback control of androgen action in male sex accessory tissues and provide a possible mechanism for weight reduction caused by Cd2+ in those organs in vivo. Competitive inhibition of binding by p-hydroxymercuribenzoate was observed. Neither this finding nor relative inhibitory effectiveness of the various metals is consistent with involvement of protein sulfhydryl groups at the binding site in the mechanism of inhibition.