Effects of Zinc on the Trophic Activity of Testosterone in Androgen Target Tissues of Castrate Mice

Abstract

Swiss, 60-day castrate mice were injected with 0.5, 1.5 or 5.0 mg of testosterone propionate (TP; single dose, subcutaneously) 5 days before sacrifice, in order to investigate the ability of the submandibular gland (SMG) and other androgen target tissues to recover their normal morphology and function. Some animals were additionally injected intraperitoneally with ZnCl2 (0.14 or 0.28 mg Zn2+/animal per day) during the last 15 days before sacrifice. Only SMG tissue fully recovered by TP treatment. ZnCl2 significantly impaired the dose-dependent recovery of the granular ducts of mouse SMG tissue and that of other organs which display 'androgenic' (prostate, epididymis) and 'anabolic' responses (bulbocavernosus muscle). Histological examination of testes and epididymides of intact mice injected with ZnCl2 revealed abnormal spermatogenesis with multinucleated cells and acidophilic bodies within the tubular lumen; the circulating levels of testosterone in these animals were low. In vitro, Zn2+ inhibited androgen-binding activity in SMG cytosol, but the binding capacity increased in SMG of zinc-injected animals. It is suggested that zinc, although essential for the androgenic expression, is critical as far as its intracellular concentrations are concerned and that pharmacological doses of Zn2+ determine androgenic suppression by competition at receptor and acceptor levels.