Endocrine disruption of the thyroid and its consequences in development

Abstract

Thyroid hormone (TH) is essential for normal human development. This is particularly true for the brain, but it is also true for other organs and systems. Despite the universally held recognition that TH is required for brain development, the specific role of TH in brain development is incompletely understood at best. In part, the difficulty in understanding the role of TH in brain development is due to the complexity of the processes whereby biologically active TH is delivered to target cells and to the complexity of TH action on its receptors. The fetus does not produce sufficient TH for its needs prior to about 20 weeks gestation in the human (about 18 days in the rodent). During this period, a complex interaction of transporters and enzymes is required to deliver TH to the fetal brain. Once at the site of action, the effects of TH are mediated by nuclear receptors that bind to DNA regulatory elements and interact with a complex of other proteins to influence the expression of specific target genes. Studies are beginning to reveal the developmental processes affected by TH and the mechanisms underlying these effects. Given the complexity of TH action on development, it is not surprising that environmental chemicals that interfere with TH action will likewise have complex effects. However, it is essential to recognize that industrial chemicals are being found that influence TH action in unexpected ways. Molecular studies that focused on polychlorinated biphenyls (PCBs), polybrominated biphenyl ethers (PBDEs), bisphenol-A (BPA), and others indicate that a number of chemicals to which the human population is routinely exposed during development can interfere both directly and indirectly with TH action, producing consequences that are not identical to thyroid disease itself. These studies have profound implications for public health and for global strategies to protect the public by applying modern science in regulatory domains charged with chemical safety. In addition, the literature describing the environmental effects of perchlorate exposure on the thyroid system may be showing us that short-term, high-dose studies to characterize the risk of adverse health outcome to these exposures are not capable of predicting the risk of long-term, low-dose exposures. Considering the importance of the thyroid system in directing development, it will be essential to clarify these issues. © Springer-Verlag Berlin Heidelberg 2011.