Thyroid system-disrupting chemicals: interference with thyroid hormone binding to plasma proteins and the cellular thyroid hormone signaling pathway.
In vertebrates, thyroid hormones are essential for post-embryonic development, such as establishing the central nervous system in mammals and metamorphosis in amphibians. The present paper summarizes the possible extra-thyroidal processes that environmental chemicals are known to or suspected to target in the thyroid hormone-signaling pathway. We describe how such chemicals interfere with thyroid-hormone-binding protein functions in plasma, thyroid-hormone-uptake system, thyroid-hormone-metabolizing enzymes, and activation or suppression of thyroid-hormone-responsive genes through thyroid-hormone receptors in mammals and amphibian tadpoles. Several organohalogens affect different aspects of the extra-thyroidal thyroid-hormone-signaling pathway but hardly affect thyroid hormone binding to receptors. Rodents and amphibian tadpoles are most sensitive to the effects of environmental chemicals during specific thyroid-hormone-related developmental windows. Possible mechanisms by which environmental chemicals exert multipotent activities beyond one hormone-signaling pathway are discussed.
Yamauchi
Kiyoshi
K
Department of Biological Science, Faculty of Science, Shizuoka University, Suruga-ku, Shizuoka, Japan. sbkyama@ipc.shizuoka.ac.jp
Ishihara
Akinori
A
D000818:Animals; D001667:Binding, Competitive; D001692:Biological Transport; D001798:Blood Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D052244:Endocrine Disruptors / Q000737:chemistry / Q000494:pharmacology*; D004785:Environmental Pollutants / Q000737:chemistry / Q000494:pharmacology*; D005786:Gene Expression Regulation; D015398:Signal Transduction / Q000187:drug effects*; D013961:Thyroid Gland / Q000187:drug effects; D013963:Thyroid Hormones / Q000378:metabolism*; D014714:Vertebrates / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*
D001798:Blood Proteins; D002352:Carrier Proteins; D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D013963:Thyroid Hormones