Role of testosterone in γ-glutamyltranspeptidase-dependent renal methylmercury uptake in mice

Toshiko Tanaka, Akira Naganuma, Nobuhiko Miura, Nobumasa Imura

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)58-63
Number of pages6
JournalToxicology and Applied Pharmacology
Volume112
Issue number1
DOIs
Publication statusPublished - 1992 Jan

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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