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Thyroid hormone-related pathways encompass the complex physiological processes involved in the synthesis, transport, metabolism, and signaling of thyroid hormones, which are essential regulators of growth, development, and energy homeostasis [3, 6]. The primary therapeutic targets within these pathways are the thyroid hormone receptors (TR-alpha and TR-beta), which act as nuclear transcription factors to control the expression of genes involved in metabolic rate and cardiovascular function [4, 10, 12]. Other critical components include the thyroid-stimulating hormone receptor (TSHR), the enzyme thyroid peroxidase (TPO), and iodothyronine deiodinases [5, 13, 14]. Drugs targeting these pathways include hormone replacements for hypothyroidism, antithyroid agents for hyperthyroidism, and selective TR-beta agonists like resmetirom for metabolic conditions such as non-alcoholic steatohepatitis (NASH) [2, 11, 12]. Dysregulation of these pathways is central to thyroid diseases and is increasingly recognized as a factor in metabolic syndrome and cardiovascular disorders [6, 14]. The term "thyroid hormone-related pathways" is also frequently used in regulatory toxicology to describe the suite of assays used to detect endocrine disruption [17, 18].
Agonism of thyroid hormone receptors to modulate gene transcription; inhibition of thyroid peroxidase to decrease hormone synthesis; inhibition of deiodinases to prevent peripheral T4 to T3 conversion.
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