scholarly journals An essential role of the Steroid receptor coactivator‐p300 pathway in thyroid hormone receptor mediated metamorphosis in Xenopus laevis

2006 ◽  
Vol 20 (5) ◽  
Author(s):  
Bindu Diana Paul ◽  
Daniel R Buchholz ◽  
Liezhen Fu ◽  
Yun‐Bo Shi
Keyword(s):  
Thyroid Hormone ◽  
Xenopus Laevis ◽  
Hormone Receptor ◽  
Essential Role ◽  
Thyroid Hormone Receptor ◽  
Steroid Receptor ◽  
Steroid Receptor Coactivator ◽  
Coactivator P300

Specificity of thyroid hormone receptor subtype and steroid receptor coactivator-1 on thyroid hormone action

2003 ◽  
Vol 284 (1) ◽  
pp. E36-E46 ◽  
Author(s):  
Peter M. Sadow ◽  
Olivier Chassande ◽  
Karine Gauthier ◽  
Jacques Samarut ◽  
Jianming Xu ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Steroid Receptor ◽  
Receptor Subtype ◽  
Thyroid Function Tests ◽  
Hormone Action ◽  
Peripheral Tissues ◽  
Steroid Receptor Coactivator ◽  
Thyroid Hormone Action

Isoforms of the thyroid hormone receptor ( TR) α and TRβ genes mediate thyroid hormone action. How TR isoforms modulate tissue-specific thyroid hormone (TH) action remains largely unknown. The steroid receptor coactivator-1 (SRC-1) is among a group of transcriptional coactivator proteins that bind to TRs, along with other members of the nuclear receptor superfamily, and modulate the activity of genes regulated by TH. Mice deficient in SRC-1 possess decreased tissue responsiveness to TH and many steroid hormones; however, it is not known whether or not SRC-1-mediated activation of TH-regulated gene transcription in peripheral tissues, such as heart and liver, is TR isoform specific. We have generated mice deficient in TRα and SRC-1, as well as in TRβ and SRC-1, and investigated thyroid function tests and effects of TH deprivation and TH treatment compared with wild-type (WT) mice or those deficient in either TR or SRC-1 alone. The data show that 1) in the absence of TRα or TRβ, SRC-1 is important for normal growth; 2) SRC-1 modulates TRα and TRβ effects on heart rate; 3) two new TRβ-dependent markers of TH action in the liver have been identified, osteopontin (upregulated) and glutathione S-transferase (downregulated); and 4) SRC-1 may mediate the hypersensitivity to TH seen in liver of TRα-deficient mice.

scholarly journals The Ability of Thyroid Hormone Receptors to Sense T4 as an Agonist Depends on Receptor Isoform and on Cellular Cofactors

2014 ◽  
Vol 28 (5) ◽  
pp. 745-757 ◽  
Author(s):  
Amy Schroeder ◽  
Robyn Jimenez ◽  
Briana Young ◽  
Martin L. Privalsky
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Hormone Receptors ◽  
Thyroid Hormone Receptor ◽  
Cell Types ◽  
Receptor Associated Protein ◽  
Steroid Receptor Coactivator ◽  
Different Cell Types

Abstract T4 (3,5,3′,5′-tetraiodo-l-thyronine) is classically viewed as a prohormone that must be converted to the T3 (3,5,3′-triiodo-l-thyronine) form for biological activity. We first determined that the ability of reporter genes to respond to T4 and to T3 differed for the different thyroid hormone receptor (TR) isoforms, with TRα1 generally more responsive to T4 than was TRβ1. The response to T4 vs T3 also differed dramatically in different cell types in a manner that could not be attributed to differences in deiodinase activity or in hormone affinity, leading us to examine the role of TR coregulators in this phenomenon. Unexpectedly, several coactivators, such as steroid receptor coactivator-1 (SRC1) and thyroid hormone receptor-associated protein 220 (TRAP220), were recruited to TRα1 nearly equally by T4 as by T3 in vitro, indicating that TRα1 possesses an innate potential to respond efficiently to T4 as an agonist. In contrast, release of corepressors, such as the nuclear receptor coreceptor NCoRω, from TRα1 by T4 was relatively inefficient, requiring considerably higher concentrations of this ligand than did coactivator recruitment. Our results suggest that cells, by altering the repertoire and abundance of corepressors and coactivators expressed, may regulate their ability to respond to T4, raising the possibility that T4 may function directly as a hormone in specific cellular or physiological contexts.

scholarly journals Essential Role of GATA2 in the Negative Regulation of Type 2 Deiodinase Gene by Liganded Thyroid Hormone Receptor β2 in Thyrotroph

PLoS ONE ◽  
2015 ◽  
Vol 10 (11) ◽  
pp. e0142400 ◽  
Author(s):  
Hideyuki Matsunaga ◽  
Shigekazu Sasaki ◽  
Shingo Suzuki ◽  
Akio Matsushita ◽  
Hirotoshi Nakamura ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Essential Role ◽  
Thyroid Hormone Receptor ◽  
Negative Regulation

scholarly journals A Quantitative High-Throughput Screen Identifies Novel Inhibitors of the Interaction of Thyroid Receptor β with a Peptide of Steroid Receptor Coactivator 2

2011 ◽  
Vol 16 (6) ◽  
pp. 618-627 ◽  
Author(s):  
Ronald L. Johnson ◽  
Jong Yeon Hwang ◽  
Leggy A. Arnold ◽  
Ruili Huang ◽  
Jennifer Wichterman ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
High Throughput ◽  
Hormone Receptor ◽  
Mammalian Cells ◽  
Thyroid Hormone Receptor ◽  
Steroid Receptor ◽  
Nuclear Hormone Receptor ◽  
High Throughput Screen ◽  
Data Set ◽  
Steroid Receptor Coactivator

The thyroid hormone receptors (TR) are members of the nuclear hormone receptor (NHR) superfamily that regulate development, growth, and metabolism. Upon ligand binding, TR releases bound corepressors and recruits coactivators to modulate target gene expression. Steroid receptor coactivator 2 (SRC2) is an important coregulator that interacts with TRβ to activate gene transcription. To identify novel inhibitors of the TRβ and SRC2 interaction, the authors performed a quantitative high-throughput screen (qHTS) of a TRβ-SRC2 fluorescence polarization assay against more than 290 000 small molecules. The qHTS assayed compounds at 6 concentrations up to 92 µM to generate titration–response curves and determine the potency and efficacy of all compounds. The qHTS data set enabled the characterization of actives for structure–activity relationships as well as for potential artifacts such as fluorescence interference. Selected qHTS actives were tested in the screening assay using fluoroprobes labeled with Texas Red or fluorescein. The retest identified 19 series and 4 singletons as active in both assays with 40% or greater efficacy, free of compound interference, and not toxic to mammalian cells. Selected compounds were tested as independent samples, and a methylsulfonylnitrobenzoate series inhibited the TRβ-SRC2 interaction with 5 µM IC50. This series represents a new class of thyroid hormone receptor–coactivator modulators.

scholarly journals A role of unliganded thyroid hormone receptor in postembryonic development in Xenopus laevis

2007 ◽  
Vol 124 (6) ◽  
pp. 476-488 ◽  
Author(s):  
Yukiyasu Sato ◽  
Daniel R. Buchholz ◽  
Bindu D. Paul ◽  
Yun-Bo Shi
Keyword(s):  
Thyroid Hormone ◽  
Xenopus Laevis ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Postembryonic Development

CBP-dependent and independent enhancing activity of steroid receptor coactivator-1 in thyroid hormone receptor-mediated transactivation

1999 ◽  
Vol 147 (1-2) ◽  
pp. 103-112 ◽  
Author(s):  
Masato Ikeda ◽  
Akio Kawaguchi ◽  
Akira Takeshita ◽  
William W. Chin ◽  
Toyoshi Endo ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Steroid Receptor ◽  
Steroid Receptor Coactivator

scholarly journals TRAM-1, A Novel 160-kDa Thyroid Hormone Receptor Activator Molecule, Exhibits Distinct Properties from Steroid Receptor Coactivator-1

1997 ◽  
Vol 272 (44) ◽  
pp. 27629-27634 ◽  
Author(s):  
Akira Takeshita ◽  
Guemalli R. Cardona ◽  
Noriyuki Koibuchi ◽  
Chen-Shian Suen ◽  
William W. Chin
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Steroid Receptor ◽  
Steroid Receptor Coactivator ◽  
Receptor Activator
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