67 - Thyroid Hormone Action

Abstract

Thyroid hormone (TH) signaling is required for both normal development in humans and normal physiologic functions in the adult. The principal effects of TH signaling are mediated by intracellular triidothyronine (T3), which interacts with TH receptor (TR) isoforms, present primarily in the nucleus. The T3–TR complex mediates the regulation of a wide array of target genes, both positively and negatively, via the interaction of the TR with DNA response elements, as well as some pathways through indirect interactions. Notably, TRs have activity in the presence or absence of ligand that is mediated by coregulatory proteins and define T3 sensitivity across tissues. The presence of TR isoforms in all cell types allows TH signaling to regulate numerous critical pathways in a variety of cell types, explaining its critical role in human physiology. Identifying the mechanisms of TH signaling is important for understanding the clinical manifestations of thyroid diseases, as well as identifying novel therapeutic targets for cardiac, neurologic, and metabolic diseases.