Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA154533 | ENA |
REPOSITORIES: ENA
Similar Datasets
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:Identical gene regulation patterns of triiodothyronine (T3) and selective thyroid hormone receptor modulator GC-1 [Illumina]
| PRJNA154535 | ENA
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
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.
2011-10-31 | GSE32444 | GEO
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.
2011-10-31 | GSE32443 | GEO
Project description:Thyroid hormone (3,5,3'-triiodothyronine, T3) sensitively influences the pituitary gland, a source of hormones that control tissues throughout the body. The underlying transcriptional response is believed to hinge crucially on interaction of T3 receptors with enhancers in the genome but it remains unknown how T3 regulates pituitary chromatin and how this regulation adjusts to hypothyroid and hyperthyroid conditions.
2023-04-17 | GSE197703 | GEO
Project description:Microarray study of iBAT gene expression comparing a) adult male offspring of control and 3,3’,5-triiodothyronine (T3)-treated mothers during pregnancy and b) adult male offspring of control and maternal thyroid hormone receptor (TR) β signaling (TRb) treated mothers during pregnancy. Microarrays were conducted by Atlas Biolabs (Berlin, Germany) on GeneChip Clariom S arrays (Affymetrix/Thermofisher, Germany).
2023-06-21 | E-MTAB-12587 | biostudies-arrayexpress
Project description:Astrocytes mediate the action of thyroid hormone in the brain on other neural cells through the production of the active hormone triiodothyronine (T3) from its precursor thyroxine (T4). T3 has also many effects on the astrocytes in vivo and in culture, but whether these actions are directly mediated by transcriptional regulation is not clear. In this work, we have analyzed the genomic response to T3 of cultured astrocytes isolated from the postnatal mouse cerebral cortex, using RNA sequencing. Cultured astrocytes express relevant genes of thyroid hormone metabolism and action encoding type 2 deiodinase (Dio2), Mct8 transporter (Slc16a2), T3 receptors (Thra1 and Thrb), and nuclear corepressor (Ncor1) and coactivator (Ncoa1). T3 changed the expression of 668 genes (4.5% of expressed genes), of which 117 genes (0.8% of expressed genes) were primary, transcriptional responses. The Wnt and Notch pathways were down-regulated at the post-transcriptional level. Comparison with the effect of T3 on astrocyte-enriched genes in mixed cerebrocortical cultures isolated from fetal cortex revealed that the response to T3 is influenced by the degree of astrocyte maturation, and that in agreement with its physiological effects, T3 promotes the transition between the fetal and adult patterns of gene expression.
2018-08-21 | GSE110372 | GEO