Citation:

Gilbert, M. The Thyroid Axis – Overview of Anatomy, Physiology, Regulation in Mammalian Systems. Thyroid Hormone Assessment: Implications for Developmental and Reproductive Toxicology, Washington, DC, May 09 - 10, 2019.

Impact/Purpose:

EPA and other international regulatory bodies have a priority to identify chemicals with potential to disrupt thyroid hormone function.A workshop sponsored by the Health and Environmental Sciences Institute (HESI) and European Teratology entitled, “Thyroid Hormone Assessment: Implications for Developmental and Reproductive Toxicology” was held in Washington DC, May 9 and 10, 2019. Updated U.S. and international guidelines and regulatory guidance require measuring thyroid hormone levels in blood, but laboratories vary widely in the methods they use to measure thyroid hormones in young rodents and their success in getting reliable data. This workshop was intended to address the state of the science, provide clarification and guidance on collection, assessment, and interpretation of thyroid hormone data for regulatory toxicology and risk assessment, and to agree on recommendations for improving understanding about thyroid changes and their relationship to adverse outcomes. Dr. Gilbert as the kick off speaker of the workshop was tasked with setting the stage for the current state of biological knowledge of the thyroid system in mammalian species.

Description:

Rodent models have been essential to our understanding of the thyroid endocrine system, elucidating the role of thyroid hormones in brain development, and the identification and characterization of potential thyroid mediated toxicities in the regulatory arena. Adverse neurodevelopmental consequences remain a primary concern when evaluating the toxicity of thyroid disrupting chemicals (TDC). Although many TDCs are identified by their ability to reduce circulating levels of thyroid hormones (TH), the inherent complexity of the thyroid system makes for a variety of potential target sites of chemical action, As the basic anatomy, physiology, and mechanisms of thyroid regulation are analogues in rodents and humans, the same sites of potential chemical interaction exist in both species. The purpose of this presentation is to provide an introduction to the basic components of the thyroid system and an overview of thyroid biology. The biological regulation and numerous compensatory mechanisms that have evolved to keep tissue level concentrations of thyroid hormone within a tight range will be reviewed. The role of thyroid hormone in brain development will be discussed with respect to our current yet incomplete state of scientific knowledge. How the rodent pregnancy model mimics the many complexities of human thyroid biology during early development will be highlighted, but instances where both qualitative and quantitative differences exist identified and discussed. An appreciation of the complexities of this endocrine system especially when coupled with its role in neurodevelopment is essential to inform our use of rodent data in human health risk assessment. Does not reflect US EPA policy.

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