ArticleThe Journal of clinical investigation2005
Negative regulation by thyroid hormone receptor requires an intact coactivator-binding surface.
Article in The Journal of clinical investigation, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- American Thyroid Association Guide to investigating thyroid hormone economy and action in rodent and cell models.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
- Thyroid hormone receptor β sumoylation is required for thyrotropin regulation and thyroid hormone production.JCI insight · 2021Article
- Nuclear Receptor Coactivators (NCOAs) and Corepressors (NCORs) in the Brain.Endocrinology · 2020Review
- The selective loss of the type 2 iodothyronine deiodinase in mouse thyrotrophs increases basal TSH but blunts the thyrotropin response to hypothyroidism.Endocrinology · 2015Article
- Thyroid hormone regulates muscle fiber type conversion via miR-133a1.The Journal of cell biology · 2014Article
- Thyroid hormone receptors and resistance to thyroid hormone disorders.Nature reviews. Endocrinology · 2014Review
- Circadian regulation of Tshb gene expression by Rev-Erbα (NR1D1) and nuclear corepressor 1 (NCOR1).The Journal of biological chemistry · 2014Article
- Thyroid hormone signaling in vivo requires a balance between coactivators and corepressors.Molecular and cellular biology · 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
- Nuclear corepressors mediate the repression of phospholipase A2 group IIa gene transcription by thyroid hormone.The Journal of biological chemistry · 2013Article
- The thyroid axis is regulated by NCoR1 via its actions in the pituitary.Endocrinology · 2012Article
- Minireview: The neural regulation of the hypothalamic-pituitary-thyroid axis.Endocrinology · 2012Review
- Genetic evidence that thyroid hormone is indispensable for prepubertal insulin-like growth factor-I expression and bone acquisition in mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2012Article
- Thyroid hormone and COUP-TF1 regulate kallikrein-binding protein (KBP) gene expression.Endocrinology · 2011Article
- Negative regulation by nuclear receptors: a plethora of mechanisms.Trends in endocrinology and metabolism: TEM · 2011Review
- The nuclear receptor corepressor (NCoR) controls thyroid hormone sensitivity and the set point of the hypothalamic-pituitary-thyroid axis.Molecular endocrinology (Baltimore, Md.) · 2011Article
- Article
- Complete activation of thyroid hormone receptor β by T3 is essential for normal cochlear function and morphology in mice.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2011Article
- A live zebrafish-based screening system for human nuclear receptor ligand and cofactor discovery.PloS one · 2010Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 4 countries.
Funding
Abstract
Thyroid hormone (TH) action is mediated by TH receptors (TRs), which are members of the nuclear hormone receptor superfamily. In vitro studies have demonstrated that TR activity is regulated by interactions with corepressor and coactivator proteins (CoRs and CoAs, respectively). TH stimulation is thought to involve dissociation of CoRs and recruitment of CoAs to the liganded TR. In contrast, negative regulation by TH is thought to occur via recruitment of CoRs to the liganded TR. The physiological role of CoAs bound to TRs, however, has yet to be defined. In this study, we used gene-targeting techniques to mutate the TR-beta locus within its activation function-2 (AF-2) domain (E457A). This mutation was chosen because it completely abolished CoA recruitment in vitro, while preserving normal triiodothyronine (T3) binding and CoR interactions. As expected, TH-stimulated gene expression was reduced in homozygous E457A mice. However, these animals also displayed abnormal regulation of the hypothalamic-pituitary-thyroid axis. Serum thyroxine, T3, and thyroid-stimulating hormone (TSH) levels and pituitary Tshb mRNA levels were inappropriately elevated compared with those of WT animals, and L-T3 treatment failed to suppress serum TSH and pituitary Tshb mRNA levels. Therefore, the AF-2 domain of TR-beta is required for positive and, paradoxically, for negative regulation by TH in vivo.
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Registered trials
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.