Integrating basic research on thyroid hormone action into screening and testing programs for thyroid disruptors

Abstract

Thyroid hormone signaling is highly conserved among all the vertebrates, and appears to be present in some invertebrates. Both the components that comprise the system and its general role in development and physiology are evolutionarily conserved, although specific events regulated by thyroid hormones, such as amphibian metamorphosis, may differ among taxonomic groups. The articles in this issue review the thyroid systems of mammals (specifically humans and rodents), fish, amphibians, and birds, and the states of the assays and endpoints used to detect disruption of the thyroid system within a toxicological paradigm. It must be noted that while reptiles represent an enormously important group, they were excluded because there was not enough information in the literature on thyroid toxicology in reptiles at the time that this series of reviews was drafted. Each review highlights the best assays for current regulatory use and those that may be considered for development for future use and research. However, it is important to remember that thyroid research is moving ahead at a fast pace. New thyroid research will impact the design of future thyroid assays used for the detection of thyroid system disruption in ways that may not be anticipated at the time of this writing. Several new areas of exploration are discussed that reveal potential sites of disruption in the thyroid system, including (1) the importance of the neural drive for TSH upregulation, (2) thyroid hormone transport, including cellular transporters like monocarboxylate anion transporter 8 (MCT8) that can regulate thyroid hormone action at the cellular level, and thyroid hormone-binding proteins in the serum that have been shown to differentially bind to environmental chemicals (e.g., certain PCB congeners), and (3) the deiodinases as a target for disruption of thyroid hormone activity in the peripheral thyroid system. The review papers in this issue represent the current state of thyroid assays and endpoints for detection of chemicals that disrupt the thyroid system.