Alternative ligands for thyroid hormone receptors

Thyroid hormone receptors (TRs) are ligand-dependent transcription factors that activate or repress gene transcription, resulting in the regulation of numerous physiological programs. While 3,3’,5-L-triiodothyronine is the TR cognate ligand, these receptors can also be activated by various alternati...

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Veröffentlicht in:Molecular and cellular endocrinology 2019-08, Vol.493, p.110448-110448, Article 110448
Hauptverfasser: Lazcano, Iván, Hernández-Puga, Gabriela, Robles, Juan Pablo, Orozco, Aurea
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Sprache:eng
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Zusammenfassung:Thyroid hormone receptors (TRs) are ligand-dependent transcription factors that activate or repress gene transcription, resulting in the regulation of numerous physiological programs. While 3,3’,5-L-triiodothyronine is the TR cognate ligand, these receptors can also be activated by various alternative ligands, including endogenous and synthetic molecules capable of inducing diverse active receptor conformations that influence thyroid hormone-dependent signaling pathways. This review mainly discusses current knowledge on 3,5-diiodo-L-thyronine and 3,5,3′-triiodothyroacetic acid, two endogenous molecules that bind to TRs and regulate gene expression; and the molecular interactions between TRs and ligands, like synthetic thyromimetics developed to target specific TR isoforms for tissue-specific regulation of thyroid-related disorders, or endocrine disruptors that have allowed the design of new analogues and revealed essential amino acids for thyroid hormone binding. •T3 is the cognate ligand for TRs, but they are also activated by various alternative ligands.•TR alternative ligands include endogenous and synthetic molecules capable of inducing diverse active receptor conformations.•TRIAC and T2 are endogenous alternative TR ligands with demonstrated biological actions that mimic T3-dependent signaling pathways.•Synthetic analogs with T3 structural similarities can selectively activate TR isoforms and their particular signaling pathways.
ISSN:0303-7207
1872-8057
DOI:10.1016/j.mce.2019.05.007