To elucidate the mechanisms responsible for sex and age differences in renal methylmercury uptake, effects of castration and testosterone treatment on mercury content and activity of renal γ-glutamyltranspeptidase (γ-GTP), which supposedly plays an important role in renal mercury, were investigated in mice. Between 2 and 8 weeks of age, renal methylmercury uptake in male mice determined 4 hr after injection of a nontoxic dose of methylmercuric chloride (MMC, 1 μmol/kg, sc) increased about fivefold. At 4 weeks of age, a significant sex difference in renal mercury uptake first appeared. Renal mercury content in 4-week-old male mice was twofold higher than that of females and increased with age, but remained constant in females. Small but significant (p < 0.05) differences in mercury content in other tissues were observed, which could not account for the marked sex- and age-related differences in renal mercury concentrations. Renal γ-GTP activity gradually increased in males with maturation, and a sexual dimorphism of renal γ-GTP was apparent after the fourth week. Seven days after castration of 4-week-old male mice, both renal mercury content and γ-GTP activity were decreased to the levels in females. Activity of γ-GTP was subsequently elevated to control male levels by sc injection of testosterone (5 mg/kg/day × 7 days). In female mice, both renal mercury content and γ-GTP activity were increased to the level of males by testosterone treatment (5 mg/kg/day × 14 days). Thus, the renal mercury content was closely correlated with changes in renal γ-GTP activity. These results suggest that sex and age differences in renal methylmercury accumulation may be due to a difference in renal γ-GTP activity controlled at least in part by testosterone.
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