ArticlePloS one2013
Gene specific actions of thyroid hormone receptor subtypes.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Molecular Determinants of Thyroid Cancer Progression: Thyroid Hormone Signaling, the BRAF/MAPK Pathway, and Emerging miRNA Biomarkers.Biomedicines · 2026Review
- Upregulation of Hepatic Glutathione S-Transferase Alpha 1 Ameliorates Metabolic Dysfunction-Associated Steatosis by Degrading Fatty Acid Binding Protein 1.International journal of molecular sciences · 2024Article
- The impact of thyroid hormone dysfunction on ischemic heart disease.Endocrine connections · 2019Review
- Protein Disulfide Isomerase Modulates the Activation of Thyroid Hormone Receptors.Frontiers in endocrinology · 2018Article
- New insights into thyroid hormone action.Pharmacology & therapeutics · 2017Review
- Thyroid Dysfunction and Heart Failure: Mechanisms and Associations.Current heart failure reports · 2017Review
- Ligand Independent and Subtype-Selective Actions of Thyroid Hormone Receptors in Human Adipose Derived Stem Cells.PloS one · 2016Article
- A thyroid hormone receptor/KLF9 axis in human hepatocytes and pluripotent stem cells.Stem cells (Dayton, Ohio) · 2015Article
- Thyroid hormone induction of human cholesterol 7 alpha-hydroxylase (Cyp7a1) in vitro.Molecular and cellular endocrinology · 2014Article
- Deciphering direct and indirect influence of thyroid hormone with mouse genetics.Molecular endocrinology (Baltimore, Md.) · 2014Review
- Cloning and identification of a novel thyroid hormone receptor β isoform expressed in the pituitary gland.Molecular and cellular biochemistry · 2014Article
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- Article
- Nuclear corepressors mediate the repression of phospholipase A2 group IIa gene transcription by thyroid hormone.The Journal of biological chemistry · 2013Article
- SIRT1 is a direct coactivator of thyroid hormone receptor β1 with gene-specific actions.PloS one · 2013Article
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There are two homologous thyroid hormone (TH) receptors (TRs α and β), which are members of the nuclear hormone receptor (NR) family. While TRs regulate different processes in vivo and other highly related NRs regulate distinct gene sets, initial studies of TR action revealed near complete overlaps in their actions at the level of individual genes. Here, we assessed the extent that TRα and TRβ differ in target gene regulation by comparing effects of equal levels of stably expressed exogenous TRs +/- T(3) in two cell backgrounds (HepG2 and HeLa). We find that hundreds of genes respond to T(3) or to unliganded TRs in both cell types, but were not able to detect verifiable examples of completely TR subtype-specific gene regulation. TR actions are, however, far from identical and we detect TR subtype-specific effects on global T(3) response kinetics in HepG2 cells and many examples of TR subtype specificity at the level of individual genes, including effects on magnitude of response to TR +/- T(3), TR regulation patterns and T(3) dose response. Cycloheximide (CHX) treatment confirms that at least some differential effects involve verifiable direct TR target genes. TR subtype/gene-specific effects emerge in the context of widespread variation in target gene response and we suggest that gene-selective effects on mechanism of TR action highlight differences in TR subtype function that emerge in the environment of specific genes. We propose that differential TR actions could influence physiologic and pharmacologic responses to THs and selective TR modulators (STRMs).
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