Vulnerability of the developing brain to thyroid abnormalities: environmental insults to the thyroid system.
Vulnerability of the developing brain to thyroid abnormalities: environmental insults to the thyroid system.
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发育中的大脑对甲状腺异常的脆弱性：对甲状腺系统的环境侮辱。
DOI：
10.1289/ehp.94102125
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发表时间：
1994-06
影响因子：
10.4
通讯作者：
中科院分区：
文献类型：
--
作者：
神经系统的发育遵循有序的模式，当甲状腺激素缺乏或过多时，这些模式会受到严重干扰。如果这发生在适当的发育期，可能导致不可逆的神经损伤。缺陷的性质取决于具体的发展时期和甲状腺功能紊乱的严重程度。多氯联苯和二恶英在结构上与甲状腺激素相似。它们的结合特征与甲状腺激素的结合特征相似，并且所有三个组都与细胞溶质Ah受体、甲状腺激素受体和血清甲状腺激素结合蛋白甲状腺素运载蛋白结合。根据毒素的剂量和使用的同类物，毒素会降低或模拟甲状腺激素的生物作用。任何一种影响，如果发生在大脑发育过程中，都可能产生灾难性的后果。在子宫内和/或婴儿时期接触多氯联苯或二恶英的儿童和动物可表现出不同程度的行为障碍。这些疾病类似于在子宫内和/或婴儿期暴露于甲状腺激素缺乏症的儿童中观察到的疾病。多氯联苯和二恶英的发育神经毒性机制尚不清楚，但数据表明，这可能部分或完全是由神经发育期间甲状腺激素的可用性和作用的改变介导的。母亲短暂暴露于目前认为对母亲无毒的毒素剂量可能会对胎儿或围产期神经发育产生影响。如果毒素通过其对甲状腺激素作用的影响而起作用，则通常不会改变胎儿发育的毒素剂量如果叠加在先前存在的母体/或胎儿甲状腺疾病上，可能会变得有害。
Neurologic development follows orderly patterns that can be severely disturbed when thyroid hormones are deficient or excessive. Should this occur at appropriate development periods, irreversible neurologic damage can result. The nature of the deficits depends upon the specific development period and the severity of the thyroid disturbance. PCBs and dioxins are structurally similar to the thyroid hormones. Their binding characteristics are similar to those of thyroid hormones and all three groups bind to the cytosolic Ah receptor, the thyroid hormone receptor and the serum thyroid hormone binding protein transthyretin. Depending upon the dose of toxin and the congener used, the toxins either decrease or mimic the biological action of the thyroid hormones. Either effect, if occurring during brain development, can have disastrous consequences. Children and animals exposed to PCBs or dioxins in utero and/or as infants can exhibit varying degrees of behavioral disorders. These disorders resemble those seen in children exposed to thyroid hormone deficiencies in utero and/or in infancy. The mechanism of developmental neurotoxicity of PCBs and dioxins is not known but data suggest it could be partially or entirely mediated by alterations in availability and action of thyroid hormones during neurological development. It is possible that transient exposure of the mother to doses of toxins presently considered nontoxic to the mother could have an impact upon fetal or perinatal neurological development. If the toxins act via their effect on thyroid hormone action, it is possible that doses of toxins that would normally not alter fetal development, could become deleterious if superimposed on a pre-existing maternal/or fetal thyroid disorder.