Molecular Pharmacology, Vol 17, 156-162, Copyright © 1980 by the American Society for Pharmacology and Experimental Therapeutics

Inhibition of Androgen-Receptor Interaction in Mouse Prostate Gland Cytosol by Divalent Metal Ions

¹ Department of Pharmacology and Toxicology, West Virginia University Medical Center, Morgantown, West Virginia 26506

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 upon 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 x 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 also 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.