Zoeller R Thomas
Biology Department and Program in Molecular and Cellular Biology, Morrill Science Center, University of Massachusetts-Amherst, Amherst, MA 01003, USA.
Mol Cell Endocrinol. 2005 Oct 20;242(1-2):10-5. doi: 10.1016/j.mce.2005.07.006.
Thyroid hormone (TH) is essential for normal brain development, but the specific actions of TH differ across developmental time and brain region. These actions of TH are mediated largely by a combination of thyroid hormone receptor (TR) isoforms that exhibit specific temporal and spatial patterns of expression during animal and human brain development. In addition, TR action is influenced by different co-factors, proteins that directly link the TR protein to functional changes in gene expression. Several recent studies now show that TRs may be unintended targets of chemicals manufactured for industrial purposes, and to which humans and wildlife are routinely exposed. Polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and bisphenol-A (BPA), and specific halogenated derivatives and metabolites of these compounds, have been shown to bind to TRs and perhaps have selective effects on TR functions. A number of common chemicals including polybrominated biphenyls (PBBs) and phthalates may also exert such effects. Considering the importance of TH in brain development, it will be important to pursue the possibilities that these chemicals - or interactions among chemical classes - are affecting children's health by influencing TH signaling in the developing brain.
甲状腺激素(TH)对正常脑发育至关重要,但其具体作用在发育阶段和脑区中存在差异。TH的这些作用主要由甲状腺激素受体(TR)亚型共同介导,这些亚型在动物和人类脑发育过程中呈现出特定的时空表达模式。此外,TR的作用还受到不同辅助因子的影响,这些蛋白质将TR蛋白与基因表达的功能变化直接联系起来。最近的几项研究表明,TRs可能是工业生产的化学物质的意外靶点,人类和野生动物经常接触到这些物质。多氯联苯(PCBs)、多溴二苯醚(PBDEs)、双酚A(BPA)以及这些化合物的特定卤代衍生物和代谢产物,已被证明可与TRs结合,并可能对TR功能产生选择性影响。包括多溴联苯(PBBs)和邻苯二甲酸盐在内的许多常见化学物质也可能产生此类影响。鉴于TH在脑发育中的重要性,探究这些化学物质或化学类别之间的相互作用是否通过影响发育中大脑的TH信号传导来影响儿童健康具有重要意义。