Involvement of Renal Gamma-Glutamyltranspeptidase in Differences in the Renal Uptake of Mercuric Mercury by Male and Female Mice of Various Strains and Ages

Toshiko Tanaka-Kagawa,^a Nobuhiko Miura,^b Kazuo Kobayashi,^a Nobumasa Imura,^a and Akira Naganuma^b

^aDepartment of Public Health and Molecular Toxicology, School of Pharmaceutical Sciences, Kitasato University, Minato-ku, Tokyo 108-8641, Japan and ^bDepartment of Molecular and Biochemical Toxicology, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan

Involvement of renal gamma-glutamyltranspeptidase (gamma-GTP) in differences in the renal uptake of Hg²⁺ by male and female mice of various ages was examined using five strains of mice, namely, BALB/cA, C57BL/6N, CBA/JN, C3H/HeN and ICR. We observed strain-related and gender-related differences in the renal accumulation of Hg²⁺ 30 min after the administration of mercuric chloride (1 mu mol/kg, s.c.). Renal gamma-GTP activity also varied among the tested strains, and the activity in males was about twice that in females. A significant correlation was recognized between renal gamma-GTP activity and the renal accumulation of Hg²⁺. Both renal uptake of Hg²⁺ and renal gamma-GTP activity increased gradually with age in male ICR mice from 2 to 8 weeks after birth but remained relatively constant in ICR females. Significant gender-related differences in both renal accumulation of Hg²⁺ and gamma-GTP activity were observed 4 weeks after birth and thereafter. Castration of male ICR mice decreased both renal accumulation of Hg²⁺ and gamma-GTP activity to the levels in females. Injection of testosterone increased both renal accumulation of Hg²⁺ and gamma-GTP activity in castrated male mice and in normal female mice to the levels in control male mice. These results suggest that strain-related, gender-related and age-related differences in the renal accumulation of Hg²⁺ in mice might be due to differences in renal gamma-GTP activity and, furthermore, that renal gamma-GTP activity might be controlled, at least to some extent, by testosterone.