Porterfield S P
Department of Physiology and Endocrinology, Medical College of Georgia, Augusta 30912.
Environ Health Perspect. 1994 Jun;102 Suppl 2(Suppl 2):125-30. doi: 10.1289/ehp.94102125.
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.
神经发育遵循有序模式，当甲状腺激素缺乏或过量时，这种模式可能会受到严重干扰。如果这种情况发生在适当的发育阶段，可能会导致不可逆转的神经损伤。缺陷的性质取决于特定的发育阶段以及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。它们的结合特性与甲状腺激素相似，这三组物质都与胞质芳烃受体、甲状腺激素受体以及血清甲状腺激素结合蛋白转甲状腺素蛋白结合。根据毒素剂量和所使用的同系物不同，这些毒素要么降低要么模拟甲状腺激素的生物作用。如果在大脑发育期间出现任何一种效应，都可能产生灾难性后果。在子宫内和/或婴儿期接触多氯联苯或二恶英的儿童和动物可能会表现出不同程度的行为障碍。这些障碍类似于在子宫内和/或婴儿期接触甲状腺激素缺乏的儿童所出现的障碍。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，它可能部分或完全由神经发育过程中甲状腺激素的可利用性和作用改变所介导。母亲短暂接触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。如果毒素通过对甲状腺激素作用的影响起作用，那么通常不会改变胎儿发育的毒素剂量，如果叠加在已有的母体/或胎儿甲状腺疾病上，可能会变得有害。
