It is well documented that thyroid hormone (TH) action is critical for normal brain development and is mediated by both nuclear and extranuclear pathways. Given this dependence, the impact of environmental endocrine disrupting chemicals that interfere with thyroid signaling is a major concern with direct implications for children's health. However, identifying thyroid disrupting chemicals in vivo is primarily reliant on serum thyroxine (T4) measurements within greater developmental and reproductive toxicity assessments. These studies do not examine known TH-dependent phenotypes in parallel, which complicates chemical evaluation. Additionally, there exist no recommendations regarding what degree of serum T4 dysfunction is adverse, and little consideration is given to quantifying TH action within the developing brain. This review summarizes current testing strategies in rodent models and discusses new approaches for evaluating the developmental neurotoxicity of thyroid disrupting chemicals. This includes assays to identify adverse cellular effects of the brain by both immunohistochemistry and gene expression, which would compliment serum T4 measures. While additional experiments are needed to test the full utility of these approaches, incorporation of these cellular and molecular assays could enhance chemical evaluation in the regulatory arena.

中文翻译：

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甲状腺干扰化学物质和发育神经毒性 - 评估激素作用的新工具和方法。

有充分证据表明，甲状腺激素 (TH) 的作用对于正常的大脑发育至关重要，并且由核通路和核外通路介导。鉴于这种依赖性，干扰甲状腺信号传导的环境内分泌干扰化学物质的影响是对儿童健康直接影响的主要问题。然而，在体内识别甲状腺干扰化学物质主要依赖于更大的发育和生殖毒性评估中的血清甲状腺素（T4）测量。这些研究没有并行检查已知的 TH 依赖性表型，这使化学评估变得复杂。此外，对于什么程度的血清 T4 功能障碍是不利的没有建议，也很少考虑量化发育中大脑内的 TH 作用。本综述总结了当前啮齿动物模型的测试策略，并讨论了评估甲状腺干扰化学物质的发育神经毒性的新方法。这包括通过免疫组织化学和基因表达来识别大脑的不良细胞效应的检测，这将补充血清 T4 测量。虽然需要额外的实验来测试这些方法的全部效用，但这些细胞和分子测定的结合可以增强监管领域的化学评估。