Abstract
3,3′,5-Triiodothyronine (T3) is an iodinated amino acid derivative, a small proportion of which is primarily synthesized on thyroglobulin molecules in the thyroid gland. T3 is an active form of thyroid hormone (TH) but less produced than thyroxine (T4). Most T3 is secondarily produced by deiodination of T4 in peripheral tissues. Physiological effects of T3 are exerted via nuclear thyroid receptors (TRs), which act as ligand-dependent transcription factors by binding TH-response elements (TREs) on regulatory regions of target genes in the nucleus and mitochondria. T3 changes gene transcription in a tissue-dependent manner, affecting growth and development in bone and central nervous system, regulation of lipid and carbohydrate metabolism, and protein breakdown. TR knock-out and knock-in studies demonstrate the failure of some TH actions in the TR subtype-specific manner.
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