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Abstract
Endocrine disrupting chemicals (EDCs) are synthetic or natural substances in the environment. EDCs have been shown to disrupt reproductive, developmental and other homeostatic systems by interfering with the synthesis, secretion, transport, metabolism and action of endogenous hormones including the thyroid hormone (TH) system. Since TH plays a critical role in brain development, the exposure to TH-system disrupting EDCs during development may have serious consequences. In this article, representative previous studies showing the effect of representative EDCs on the TH system are summarized. Then, the molecular mechanisms of action of polychlorinated biphenyls and polybrominated diphenyl ethers on the TH system are discussed further. Particularly, the effect of polychlorinated biphenyls and polybrominated diphenyl ethers on TH-mediated brain development is discussed. Our recent studies may provide a novel idea regarding the effect of EDCs on the TH system.
Financial & competing interest disclosure
This work was partly supported by a grant-in-aid (EXTEND2010) from Ministry of the Environment, Japan. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Key issues
Endocrine disrupting chemicals (EDCs) are both synthetic and naturally occurring substances that abound in our environment.
Many EDCs have long half-lives and can bioaccumulate in the environment, wildlife and humans.
Each EDC may act at multiple sites and via multiple pathways on the thyroid hormone system.
A window of vulnerability (developmental critical period) to EDCs may exist, and neonates and children are at the greatest risk from the negative impact of EDCs on normal thyroid functions.
Most EDCs may exhibit the ‘low-dose effect’, where doses below the range typically used in toxicological studies may disrupt hormone actions.
EDCs such as hydroxylated-polychlorinated biphenyls and hydroxylated-polybrominated diphenyl ethers metabolites share structural similarity to thyroid hormone, and perinatal exposure to such EDCs may cause abnormal brain development as similarly observed in perinatal hypothyroidism.