Mori Kouki, Yoshida Katsumi, Hoshikawa Saeko, Ito Sadayoshi, Yoshida Minoru, Satoh Masahiko, Watanabe Chiho
Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-Machi, Sendai, Japan.
Toxicology. 2006 Nov 10;228(1):77-84. doi: 10.1016/j.tox.2006.08.017. Epub 2006 Aug 22.
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.
围产期暴露于镉（Cd）或甲基汞（MeHg）会导致神经发育受损。甲状腺激素对正常脑发育至关重要。然而，Cd或MeHg，尤其是低剂量时，是否会干扰甲状腺激素作用这一问题仍有待研究。在本研究中，使用金属硫蛋白I和II（MT-I/II）基因敲除或野生型新生小鼠，研究了围产期暴露于低水平Cd或MeHg对甲状腺激素代谢的影响。从妊娠第0天至出生后第10天（PND 10），给孕鼠饮用含10 mg/L Cd的水或喂食含5 mg/kg MeHg的食物。在PND 10收集新生小鼠的血清、肝脏和大脑。测量了碘甲状腺原氨酸脱碘酶活性和血清甲状腺素（T4）浓度。无论MT基因型如何，暴露于MeHg均未引起血清T4水平、肝脏1型脱碘酶（D1）和脑2型脱碘酶（D2）活性的变化。然而，暴露于MeHg导致MT-I/II基因敲除和野生型新生小鼠脑3型脱碘酶（D3）活性降低。相比之下，暴露于Cd导致MT-I/II基因敲除新生小鼠血清T4水平降低。同样，暴露于Cd的MT-I/II基因敲除新生小鼠脑D2活性增加。给予Cd未引起肝脏D1和脑D3活性的显著变化。我们的研究表明，围产期暴露于低剂量的Cd或MeHg可引起新生小鼠脑脱碘酶活性的变化，提示胎儿和新生儿的甲状腺激素代谢可能是Cd和MeHg的潜在作用靶点。
