Effects of perinatal exposure to low doses of cadmium or methylmercury on thyroid hormone metabolism in metallothionein-deficient mouse neonates.
Perinatal exposure to cadmium (Cd) or methylmercury (MeHg) results in impaired neurodevelopment. Thyroid hormone is essential for normal brain development. However, the issue whether Cd or MeHg, especially at low doses, interrupts thyroid hormone action remains to be investigated. In the present study, effects of perinatal exposure to low levels of Cd or MeHg on thyroid hormone metabolism were examined using metallothionein I and II (MT-I/II) null or wild-type neonatal mice. Dams were exposed to 10 mg/L water of Cd or 5 mg/kg chow of MeHg from gestational day 0 to post-natal day 10 (PND 10). Sera, livers and brains were collected from neonates on PND 10. Iodothyronine deiodinase activities and serum thyroxine (T4) concentrations were measured. MeHg exposure failed to induce changes in serum T4 levels and liver type 1 deiodinase (D1) and brain type 2 deiodinase (D2) activities regardless of the MT genotype. However, exposure to MeHg resulted in a decrease in brain type 3 deiodinase (D3) activity in MT-I/II null and wild-type neonates. In contrast, exposure to Cd resulted in a decrease in serum T4 levels in MT-I/II null neonates. Consistently, brain D2 activity was increased in Cd-exposed MT-I/II null neonates. No significant changes in liver D1 and brain D3 activities were induced by Cd administration. Our study demonstrates that perinatal exposure to low doses of Cd or MeHg can induce changes in brain deiodinase activities in the neonates, suggesting that thyroid hormone metabolism in fetuses and neonates might be a potential target of Cd and MeHg.
Mori
Kouki
K
Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-Machi, Sendai, Japan. kokimori@mail.tains.tohoku.ac.jp
Yoshida
Katsumi
K
Hoshikawa
Saeko
S
Ito
Sadayoshi
S
Yoshida
Minoru
M
Satoh
Masahiko
M
Watanabe
Chiho
C
D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002104:Cadmium / Q000493:pharmacokinetics / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D007453:Iodide Peroxidase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D018811:Maternal Exposure; D008668:Metallothionein / Q000172:deficiency* / Q000235:genetics; D008767:Methylmercury Compounds / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011247:Pregnancy; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism*
D004785:Environmental Pollutants; D008767:Methylmercury Compounds; D013963:Thyroid Hormones; D002104:Cadmium; D008668:Metallothionein; D007453:Iodide Peroxidase