Porterfield S P
Medical College of Georgia, Augusta, Georgia, USA.
Environ Health Perspect. 2000 Jun;108 Suppl 3(Suppl 3):433-8. doi: 10.1289/ehp.00108s3433.
Certain polyhalogenated aromatic hydrocarbons such as polychlorinated biphenyls (PCBs) and dibenzo-p-dioxins (dioxins, 2,3,7, 8-tetrachlorodibenzo-p-dioxin) have been shown to have neurotoxic effects and to alter thyroid function during critical periods of thyroid hormone-dependent brain development. This has led to the suggestion that some of the neurotoxic effects of these compounds could be mediated through the thyroid system. Thyroid hormones are essential for normal brain development during a critical period beginning in utero and extending through the first 2 years postpartum. They regulate neuronal proliferation, migration, and differentiation in discrete regions of the brain during definitive time periods. Even transient disruption of this normal pattern can impair brain development. Thyroid hormones are necessary for normal cytoskeletal assembly and stability and the cytoskeletal system is essential for migration and neuronal outgrowth. In addition, they regulate development of cholinergic and dopaminergic systems serving the cerebral cortex and hippocampus. Animals perinatally exposed to certain environmental organohalogens such as many of the PCBs and dioxins have abnormal thyroid function and neurologic impairment. Although there are both species and congener variabilities, most reports show exposure results in thyroid enlargement and reduced serum T(4) levels with normal T(3) levels. Initial research concentrated on studying the direct actions of xenobiotics on the thyroid; however, some of these compounds bear a structural resemblance to the natural thyroid hormones and have high affinity with thyroid hormone-binding proteins such as transthyretin. These compounds could act as agonists or antagonists for receptors of the thyroid/steroid/retinoic acid superfamily. These structurally similar organohalogens could act at multiple points to alter thyroid hormone action. The similarity of the neurologic impairment seen in thyroid disorders to that seen following PCB or dioxin exposure suggests that one mechanism of neurotoxicity of these compounds could involve interaction with the thyroid system.
某些多卤代芳烃，如多氯联苯（PCBs）和二苯并 - p - 二恶英（二恶英，2,3,7,8 - 四氯二苯并 - p - 二恶英），已被证明在甲状腺激素依赖的脑发育关键期具有神经毒性作用并改变甲状腺功能。这引发了一种观点，即这些化合物的某些神经毒性作用可能通过甲状腺系统介导。甲状腺激素对于从子宫内开始并持续到产后头两年的关键期正常脑发育至关重要。它们在特定时间段调节大脑不同区域的神经元增殖、迁移和分化。即使这种正常模式的短暂中断也会损害脑发育。甲状腺激素对于正常的细胞骨架组装和稳定性是必需的，而细胞骨架系统对于迁移和神经元生长至关重要。此外，它们调节服务于大脑皮层和海马体的胆碱能和多巴胺能系统的发育。围产期接触某些环境有机卤化物（如许多多氯联苯和二恶英）的动物具有异常的甲状腺功能和神经损伤。尽管存在物种和同系物差异，但大多数报告显示接触会导致甲状腺肿大和血清T(4)水平降低，而T(3)水平正常。最初的研究集中在研究外源性物质对甲状腺的直接作用；然而，这些化合物中的一些与天然甲状腺激素具有结构相似性，并且与甲状腺激素结合蛋白如转甲状腺素蛋白具有高亲和力。这些化合物可以作为甲状腺/类固醇/视黄酸超家族受体的激动剂或拮抗剂。这些结构相似的有机卤化物可以在多个点发挥作用以改变甲状腺激素的作用。甲状腺疾病中所见的神经损伤与多氯联苯或二恶英接触后所见的神经损伤相似，这表明这些化合物神经毒性的一种机制可能涉及与甲状腺系统的相互作用。
