Role of testosterone in gamma-glutamyltranspeptidase-dependent renal methylmercury uptake in mice.

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 gamma-glutamyltranspeptidase (gamma-GTP), which supposedly plays an important role in renal mercury uptake, 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 mumol/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 less than 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 gamma-GTP activity gradually increased in males with maturation, and a sexual dimorphism of renal gamma-GTP was apparent after the fourth week. Seven days after castration of 4-week-old male mice, both renal mercury content and gamma-GTP activity were decreased to the levels in females. Activity of gamma-GTP was subsequently elevated to control male levels by sc injection of testosterone (5 mg/kg/day x 7 days). In female mice, both renal mercury content and gamma-GTP activity were increased to the level of males by testosterone treatment (5 mg/kg/day x 14 days). Thus, the renal mercury content was closely correlated with changes in renal gamma-GTP activity. These results suggest that sex and age differences in renal methylmercury accumulation may be due to a difference in renal gamma-GTP activity controlled at least in part by testosterone.