SummaryThis study explores the effects of several divalent metal ions on the in vitro production of cyclic AMP, cyclic GMP, and testosterone by rat testicular tissue and on the amount of binding of ['251]human chorionic gonadotropin (hCG) in the testis. Zn2+ at concentrations of to M enhanced the hCG-stimulated production of cyclic AMP and testosterone, but only in the presence of Ca2+. ['251]hCG binding to rat testicular tissue was not affected by Zn2+. Cu2+, Ni2+, Co2+, and MnZ+ did not increase cyclic AMP or testosterone production in concentrations of lo-' to M and even inhibited them at a high concentration M). Cyclic GMP production was not affected by these divalent ions. These results suggest that Zn2+ may play an important role in rat testicular steroidogenesis. Abbreviations hCG, human chorionic gonadotropin KRBB, Krebs Ringer bicarbonate buffer PBS, phosphate buffered saline Trace metal ions are known to influence hormones at several stages of action, including hormone secretion and activity and binding to target tissue. Conversely, hormones influence trace metal ion metabolism at several levels, including excretion and transport of ions (9). Zinc ion plays an important role in growth and sexual development. A deficiency of zinc not only reduces zinc levels in the reproductive tissues but also impairs the responsiveness of the Leydig cells to gonadotropins, and thus may cause primary hypogonadism in humans as well as in experimental animals (1, 14, 28). Furthermore, constitutionally short boys at Tanner stages 1 and 2 have lower zinc levels in their serum and hair and lower serum testosterone levels than those at Tanner stages 3 to 5 (3). These results suggest that the relative testosterone deficiency in constitutional growth delay may result in decreased zinc levels, which in turn could cause a further delay in sexual development and growth.Recent studies indicate that the uptake of hCG in the testes of zinc-injected rats is significantly higher than that in controls (1 1, 12) and that Zn2+ affects adenylate cyclase activity in bovine and human sperm (2, 8) and liver (16). We investigated that the effects of various divalent metal ions, including Zn2+, on cyclic AMP, cyclic GMP, and testosterone production stimulated by hCG and the effect of Zn2+ on the binding of [1251]hCG to rat testicular tissue in vitro.
MATERIALS AND METHODSMale Wistar rats were reared in individual stainless steel cages and fed an adequate amount of zinc (43 ppm) ad libitum for 4 wk before the study. Deionized water was also provided ad libitum. The mean weight was 242 + 16 g at the time of study.They were anesthetized with ether. Both testes were removed, decapsulated, and sectioned into 50-mg slices from one rat for each experiment. Four tissue slices from each rat were used for each concentration of each metal in the presence or absence of hCG. Studies were repeated at least once and similar results were obtained in each metal experiment. This paper describes one of three similar zinc experiments. Sixteen rats were used in al...