Thyroid-Disrupting Chemicals as Developmental Neurotoxicants

Abstract Thyroid function and action in tissues is maintained by dynamic interrelationship between the function of the hypothalamus–pituitary–thyroid axis, serum transport, cellular uptake and metabolism, and elimination via liver conjugation. Disruption of this tight balance during development results in permanent neurological deficits that can be attributed to defects in nervous system development such as neuronal migration in the developing cerebral cortex, gliogenesis and myelination, cerebellar maturation, and cochlear maturation and auditory function. Considering this, there is concern that environmental chemicals can target the thyroid gland and perturb thyroid hormone-mediated development. Over the past few decades, studies in humans and experimental animals have provided strong evidence that chemicals released into the environment can perturb the thyroid system. Therefore, the goal of this chapter is to articulate the complexities of thyroid hormone (TH) action in development and assimilate our current understanding of how thyroid toxicants may disrupt brain development. It begins by discussing the regulation of TH action and then addresses the potential points of thyroid disruption. Finally, it concludes by discussing the consequences of disruption of TH action by thyroid toxicants on the developing brain, by focusing on well-understood TH-mediated developmental processes.