Thyroid hormone-regulated chromatin and transcriptional sensitivity of the pituitary gland
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE197703 | GEO | 2023/04/17
REPOSITORIES: GEO
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Project description:Human iPSC were differentiated to hepatocytes and treated with T3 or vehicle then total RNA was sequenced. The cistrome of TRB1 or ChREBP was delineated in liver of hypothyroid and hyperthyroid mice.
2021-11-16 | GSE133110 | GEO
Project description:Hypothyroids wild type and TRbeta -/- mice were treated with T3 and livers were collected and analysed using a microarray with 6500 cDNA probes. Expression ratios were calulated between 1) hypothyroids WT and TRbeta-/- mice 2) hypothyroid WT and hypothyroid TR beta-/- mice treated with T3 and 3) hypothyroid TRbeta-/- and hypothyroid TRbeta-/- treated with T3. Keywords: other
2005-05-04 | GSE2490 | GEO
Project description:Background: Sex and age have substantial influence on thyroid function. Sex influences the risk and clinical expression of thyroid disorders (TDs), with age a proposed trigger for the development of TDs. Cardiac function is affected by thyroid hormone levels with gender differences. Accordingly, we investigated the proteomic changes involved in sex based cardiac responses to thyroid dysfunction in elderly mice. Methods: Aged (18-20 months) male and female C57BL/6 mice were fed diets to create euthyroid, hypothyroid, or hyperthyroid states. Serial echocardiographs were performed to assess heart function. Proteomic changes in cardiac protein profiles were assessed by 2-D DIGE and LC-MS/MS, and a subset confirmed by immunoblotting. Results: Serial echocardiographs showed ventricular function remained unchanged regardless of treatment. Heart rate and size increased (hyperthyroid) or decreased (hypothyroid) independent of sex. Pairwise comparison between the six groups identified 55 proteins (≥ 1.5-fold difference and p < 0.1). Compared to same-sex controls 26/55 protein changes were in the female hypothyroid heart, whereas 15/55 protein changes were identified in the male hypothyroid, and male and female hyperthyroid heart. The proteins mapped to oxidative phosphorylation, tissue remodeling and inflammatory response pathways. Conclusion: We identified both predicted and novel proteins with gender specific differential expression in response to thyroid hormone status, providing a catalogue of proteins associated with thyroid dysfunction. Pursuit of these proteins and their involvement in cardiac function will expand our understanding of mechanisms involved in sex-based cardiac response to thyroid dysfunction.
2020-12-23 | PXD022557 | Pride
Project description:The thyroid hormone receptor (TR) has been proposed to regulate target genes in the absence of triiodothyronine (T3), through the recruitment of the corepressors, NCoR and SMRT. NCoR and SMRT may thus play a key role in both hypothyroidism and resistance to thyroid hormone, though this has never been tested in vivo. To accomplish this we developed mice that express in the liver a NCoR protein (L-NCoR∆ID) that cannot interact with the TR. L-NCoR∆ID mice develop normally, however when made hypothyroid the repression of many positively regulated T3-target genes is abrogated, demonstrating that NCoR plays a specific and sufficient role in repression by the unliganded TR. Remarkably, in the euthyroid state, expression of many T3-targets are also upregulated in L-NCoR∆ID mice, demonstrating that NCoR also determines the magnitude of the response to T3 in euthyroid animals. While positive T3 targets were upregulated in L-NCoR∆ID mice in the hypo and euthyroid state there was less effect seen on negatively regulated T3 target genes. Thus, NCoR is a specific regulator of T3-action in vivo and mediates the activity of the unliganded TR. Furthermore, NCoR may play a key role in determining the differences in individual responses to similar levels of circulating T3. Keywords: NCoR, thyroid hormone signaling, mouse liver, DNA Microarray To better assess the role of NCoR in positive and negative regulation we performed micorarray analysis of gene expression in the livers of euthyroid and hypothyroid control and L-NCoR∆ID mice.
2008-12-03 | E-GEOD-10001 | biostudies-arrayexpress
Project description:Hypothyroids wild type and TRbeta -/- mice were treated with T3 and livers were collected and analysed using a microarray with 6500 cDNA probes. Expression ratios were calulated between 1) hypothyroids WT and TRbeta-/- mice 2) hypothyroid WT and hypothyroid TR beta-/- mice treated with T3 and 3) hypothyroid TRbeta-/- and hypothyroid TRbeta-/- treated with T3.
2010-06-10 | E-GEOD-2490 | biostudies-arrayexpress
Project description:The thyroid hormone receptor (TR) has been proposed to regulate target genes in the absence of triiodothyronine (T3), through the recruitment of the corepressors, NCoR and SMRT. NCoR and SMRT may thus play a key role in both hypothyroidism and resistance to thyroid hormone, though this has never been tested in vivo. To accomplish this we developed mice that express in the liver a NCoR protein (L-NCoR∆ID) that cannot interact with the TR. L-NCoR∆ID mice develop normally, however when made hypothyroid the repression of many positively regulated T3-target genes is abrogated, demonstrating that NCoR plays a specific and sufficient role in repression by the unliganded TR. Remarkably, in the euthyroid state, expression of many T3-targets are also upregulated in L-NCoR∆ID mice, demonstrating that NCoR also determines the magnitude of the response to T3 in euthyroid animals. While positive T3 targets were upregulated in L-NCoR∆ID mice in the hypo and euthyroid state there was less effect seen on negatively regulated T3 target genes. Thus, NCoR is a specific regulator of T3-action in vivo and mediates the activity of the unliganded TR. Furthermore, NCoR may play a key role in determining the differences in individual responses to similar levels of circulating T3. Keywords: NCoR, thyroid hormone signaling, mouse liver, DNA Microarray
2008-12-04 | GSE10001 | GEO
Project description:Aim. Hyperthyroidism reduces the oxidative capacity of skeletal muscle (SKM) and promotes development of a glycolytic phenotype by altering the expression of metabolic proteins. Our previous results showed that smoothelin-like protein 1 (SMTNL1), a transcriptional coregulator, promotes insulin sensitivity in SKM. Our aim was to elucidate the role of SMTNL1 in SKM under physiological and pathological 3,3′,5-Triiodo-L-thyronine (T3) concentrations. Methods. Human hyper- and euthyroid SKM biopsies were used for microarray analysis and phospho-kinase arrays. Physiological and hyperthyroid concentrations of T3 were applied on differentiated C2C12 cells upon SMTNL1 overexpression to assess the activity and expression level of the element of insulin signaling. Real-time metabolic measurements of oxygen consumption rate and extracellular acidification rate were measured. Results. Expression of genes related to energy production, nucleic acid- and lipid metabolism were changed significantly in hyperthyroid samples. SMTNL1 expression decreased in the hyperthyroid samples and in T3 treated C2C12 cells. SMTNL1 regulated muscle cell differentiation and compensated for the glycolytic shift in SKM triggered by pathological T3 exposure. Moreover, it selectively regulated TR expression at the transcriptional level. T3 excess triggered the development of insulin resistance while overexpression of SMTNL1 induced insulin sensitivity through the inhibition of JNK activity and hampered the non-genomic effects of T3 by decreasing the activity of ERK1/2 through PKC. SMTNL1 overexpression induced GLUT4 expression in hyperthyroid model to restore the normal responsiveness of glucose transport to insulin. SMTNL1 regulated glucose phosphorylation and balances glycolysis and glycogen synthesis via the downregulation of hexokinase II. T3 overload strongly increased the rate of lactate production, while SMTNL1 overexpression antagonizes the T3 effects. Conclusion. These lines of evidence suggest that SMTNL1 potentially prevents hyperthyroidism-induced changes in SKM and it holds great promise as a novel therapeutic target. Smoothelin-like Protein 1 in Hyperthyroidism
2021-10-27 | GSE178996 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE32443: Identical gene regulation patterns of triiodothyronine (T3) and selective thyroid hormone receptor modulator GC-1 [Affymetrix] GSE32444: Identical gene regulation patterns of triiodothyronine (T3) and selective thyroid hormone receptor modulator GC-1 [Illumina] Refer to individual Series
2011-10-31 | E-GEOD-32445 | biostudies-arrayexpress
Project description:Synthetic selective thyroid hormone (TH) receptor (TR) modulators (STRMs) exhibit beneficial effects on dyslipidemias in animals and humans and reduce obesity, fatty liver and insulin resistance in preclinical animal models. STRMs differ from native THs in preferential binding to the TRβ subtype versus TRα, increased uptake into liver and reduced uptake into other tissues. However, selective modulators of other nuclear receptors (NRs) exhibit important gene-selective actions which have been attributed to differential effects on receptor conformation and dynamics and these effects can have profound influences in animals and humans. While there are suggestions that STRMs could exhibit such gene-specific actions, the extent to which these effects are actually observed in vivo has not been explored. Here, we show that saturating concentrations of the main active form of TH, triiodothyronine (T3), and the prototype STRM GC-1 induce identical gene-sets in livers of euthyroid and hypothyroid mice and a human cultured hepatoma cell line that only expresses TRβ, HepG2. We find one case in which GC-1 exhibits a modest gene-specific reduction in potency versus T3, at angiopoietin-like factor 4 (ANGPTL4) in HepG2. Investigation of the latter effect confirms that GC-1 acts through TRβ to directly induce this gene. However, this gene-selective GC-1 activity is not related to unusual T3 response element (TRE) sequence, unlike previously documented promoter-selective STRM actions. Together, our data suggest that T3 and GC-1 exhibit almost identical gene regulation properties and that gene-selective actions of GC-1 and similar STRMs will be subtle and rare. We treated HepG2 with vehicle or 10nM ligand (T3 or GC1; n=3 / treatment), analyzing mRNA 24h post treatment [Affymetrix]. We also treated 9-week old euthyroid male C57/Bl6 mice with vehicle or ligand (T3 or GC-1) by a single oral gavage (n=5 per treatment) and also performed a similar study in which mice were first made hypothyroid by two week feeding on iodine deficient diet (n=3-4 per treatment), analyzing mRNA 24h post treatment [Illumina].
2011-10-31 | E-GEOD-32443 | biostudies-arrayexpress
Project description:Synthetic selective thyroid hormone (TH) receptor (TR) modulators (STRMs) exhibit beneficial effects on dyslipidemias in animals and humans and reduce obesity, fatty liver and insulin resistance in preclinical animal models. STRMs differ from native THs in preferential binding to the TR? subtype versus TR?, increased uptake into liver and reduced uptake into other tissues. However, selective modulators of other nuclear receptors (NRs) exhibit important gene-selective actions which have been attributed to differential effects on receptor conformation and dynamics and these effects can have profound influences in animals and humans. While there are suggestions that STRMs could exhibit such gene-specific actions, the extent to which these effects are actually observed in vivo has not been explored. Here, we show that saturating concentrations of the main active form of TH, triiodothyronine (T3), and the prototype STRM GC-1 induce identical gene-sets in livers of euthyroid and hypothyroid mice and a human cultured hepatoma cell line that only expresses TR?, HepG2. We find one case in which GC-1 exhibits a modest gene-specific reduction in potency versus T3, at angiopoietin-like factor 4 (ANGPTL4) in HepG2. Investigation of the latter effect confirms that GC-1 acts through TR? to directly induce this gene. However, this gene-selective GC-1 activity is not related to unusual T3 response element (TRE) sequence, unlike previously documented promoter-selective STRM actions. Together, our data suggest that T3 and GC-1 exhibit almost identical gene regulation properties and that gene-selective actions of GC-1 and similar STRMs will be subtle and rare. We treated 9-week old euthyroid male C57/Bl6 mice with vehicle or ligand (T3 or GC-1) by a single oral gavage (n=5 per treatment) and also performed a similar study in which mice were first made hypothyroid by two week feeding on iodine deficient diet (n=3-4 per treatment), analyzing mRNA 24h post treatment [Illumina]. We also treated HepG2 with vehicle or 10nM ligand (T3 or GC1; n=3 / treatment), analyzing mRNA 24h post treatment [Affymetrix].
2011-10-31 | E-GEOD-32444 | biostudies-arrayexpress