ArticleProceedings of the National Academy of Sciences of the United States of America2009
A thyroid hormone receptor mutation that dissociates thyroid hormone regulation of gene expression in vivo.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 2 of them syntheses that pooled it.
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Who cites it
30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 81 citations in OpenAlex.
- Quantitative assessment of preoperative serum thyrotropin level and thyroid cancer.Oncotarget · 2016Pooled it
- Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement.Thyroid : official journal of the American Thyroid Association · 2014Guideline
- Thyroid Hormone Action by Genomic and Nongenomic Molecular Mechanisms.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Retrospective analysis and literature review of four cases of thyroid hormone resistance syndrome caused byTranslational pediatrics · 2022Article
- TRα2-An Untuned Second Fiddle or Fine-Tuning Thyroid Hormone Action?International journal of molecular sciences · 2022Review
- Thyroid hormone receptor phosphorylation regulates acute fasting-induced suppression of the hypothalamic-pituitary-thyroid axis.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Thyroid hormone receptor β sumoylation is required for thyrotropin regulation and thyroid hormone production.JCI insight · 2021Article
- Resistance to Thyroid Hormone Beta: A Focused Review.Frontiers in endocrinology · 2021Review
- Mutational Landscape of Resistance to Thyroid Hormone Beta (RTHβ).Molecular diagnosis & therapy · 2019Review
- Thyroid Hormone Hyposensitivity: From Genotype to Phenotype and Back.Frontiers in endocrinology · 2019Review
- The actions of thyroid hormone signaling in the nucleus.Molecular and cellular endocrinology · 2017Review
- Naturally Occurring Amino Acids in Helix 10 of the Thyroid Hormone Receptor Mediate Isoform-Specific TH Gene Regulation.Endocrinology · 2017Article
- New insights into thyroid hormone action.Pharmacology & therapeutics · 2017Review
- Syndrome of Reduced Sensitivity to Thyroid Hormones: Two Case Reports and a Literature Review.Case reports in endocrinology · 2016Article
- Thyroid hormone receptors and resistance to thyroid hormone disorders.Nature reviews. Endocrinology · 2014Review
- Article
- Circadian regulation of Tshb gene expression by Rev-Erbα (NR1D1) and nuclear corepressor 1 (NCOR1).The Journal of biological chemistry · 2014Article
- Novel mechanism of positive versus negative regulation by thyroid hormone receptor β1 (TRβ1) identified by genome-wide profiling of binding sites in mouse liver.The Journal of biological chemistry · 2014Article
- Both estrogen receptor α and β stimulate pituitary GH gene expression.Molecular endocrinology (Baltimore, Md.) · 2014Article
- The syndromes of reduced sensitivity to thyroid hormone.Biochimica et biophysica acta · 2013Review
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Resistance to thyroid hormone (RTH) is most often due to point mutations in the beta-isoform of the thyroid hormone (TH) receptor (TR-beta). The majority of mutations involve the ligand-binding domain, where they block TH binding and receptor function on both stimulatory and inhibitory TH response elements. In contrast, a few mutations in the ligand-binding domain are reported to maintain TH binding and yet cause RTH in certain tissues. We introduced one such naturally occurring human RTH mutation (R429Q) into the germline of mice at the TR-beta locus. R429Q knock-in (KI) mice demonstrated elevated serum TH and inappropriately normal thyroid-stimulating hormone (TSH) levels, consistent with hypothalamic-pituitary RTH. In contrast, 3 hepatic genes positively regulated by TH (Dio1, Gpd1, and Thrsp) were increased in R429Q KI animals. Mice were then rendered hypothyroid, followed by graded T(3) replacement. Hypothyroid R429Q KI mice displayed elevated TSH subunit mRNA levels, and T(3) treatment failed to normally suppress these levels. T(3) treatment, however, stimulated pituitary Gh levels to a greater degree in R429Q KI than in control mice. Gsta, a hepatic gene negatively regulated by TH, was not suppressed in R429Q KI mice after T(3) treatment, but hepatic Dio1 and Thrsp mRNA levels increased in response to TH. Cardiac myosin heavy chain isoform gene expression also showed a specific defect in TH inhibition. In summary, the R429Q mutation is associated with selective impairment of TH-mediated gene repression, suggesting that the affected domain, necessary for TR homodimerization and corepressor binding, has a critical role in negative gene regulation by TH.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.