Environmental chemicals impacting the thyroid: targets and consequences.
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 cofactors, proteins that directly link the TR protein to functional changes in gene expression. Considering the importance of TH signaling in development, it is important to consider environmental chemicals that may interfere with this signaling. Recent research indicates that environmental chemicals can interfere with thyroid function and with TH signaling. The key issues are to understand the mechanism by which these chemicals act and the dose at which they act, and whether adaptive responses intrinsic to the thyroid system can ameliorate potential adverse consequences (i.e., compensate). In addition, several recent studies show that TRs may be unintended targets of chemicals manufactured for industrial purposes to which humans and wildlife are routinely exposed. Polychlorinated biphenyls, polybrominated diphenyl ethers, bisphenol-A, 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 and phthalates, may also exert such effects. When we consider 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.
Zoeller
R Thomas
RT
Biology Department, Program in Molecular and Cellular Biology, Morrill Science Center, University of Massachusetts-Amherst, Amherst, Massachusetts 01003, USA. tzoeller@bio.umass.edu
D000818:Animals; D001559:Benzhydryl Compounds; D001921:Brain / Q000254:growth & development; D004785:Environmental Pollutants / Q000494:pharmacology*; D005260:Female; D006801:Humans; D010636:Phenols / Q000009:adverse effects; D011075:Polybrominated Biphenyls / Q000009:adverse effects; D011078:Polychlorinated Biphenyls / Q000009:adverse effects; D011247:Pregnancy; D011988:Receptors, Thyroid Hormone / Q000187:drug effects; D013961:Thyroid Gland / Q000187:drug effects* / Q000502:physiology; D013963:Thyroid Hormones / Q000097:blood; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004785:Environmental Pollutants; D010636:Phenols; D011075:Polybrominated Biphenyls; D011078:Polychlorinated Biphenyls; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; C006780:bisphenol A; D000098826:Bisphenol A Compounds