Investigation of thyroid hormone induced gene expression in liver tissue of different thyroid hormone receptor mutants
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PRJNA362619PRJNA414077
ORGANISM(S): Mus musculus
PROVIDER: GSE93864 | GEO | 2018/02/01
REPOSITORIES: GEO
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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: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:Using tadpoles mutant for thyroid hormone receptor alpha (thra), we show that TRa is required for thyroid hormone (T3) induction of cell proliferation in the brain. RNA-sequencing showed that the TRa is required for 95% of the gene regulation responses to T3.
2019-05-13 | GSE130816 | GEO
Project description:MicroRNAs (miRNAs) are extensively in diverse biological processes. However, very little is known about the role of miRNAs in mediating thyroid hormones (TH) action. Maintenance of appropriate TH levels is known to be critically important for development, differentiation and maintenance of metabolic balance in mammals. We induced transient hypothyroidism in juvenile mice by short term exposure to methimazole and perchlorate from post natal day (PND) 12 to 15. The expression of miRNAs in the liver was analyzed with the Taqman Low Density Array (containing up to 600 rodent microRNAs). We found the expression of 40 miRNAs was significantly altered in the liver of hypothyroid mice compared to euthyroid controls. Among the miRNAs, miR-1/206/133 exhibited a massive increase in expression (50 – 500 folds). To further explore TH effect on miR-1/206/133, we treated mouse hepatocyte AML 12 cells with 10 nm T3 for 1 hr and 24 hrs. TH treatment induced the down-regulation of miR-1/206/133b at both time points, reaching statistical significance at 24 hrs. To identify the genes targeted by these miRNAs, DNA microarrays were used to examine hepatic mRNA levels in the hypothyroid mouse model alongside controls. We found transcripts from 92 known genes were significantly altered in hypothyroid mice. Web-based target predication softwares (TargetScan and Microcosm) identified 14 of these transcripts as targets of miR-1/106/133. The vast majority of these mRNA targets were significantly down-regulated in hypothyroid mice, corresponding well with the up-regulation of miR-1/206/133 in hypothyroid mouse liver. The results suggest that TH regulation of these genes may occur secondarily via the reduced repression consequent to TH-induced down-regulation of miR-1/206/133. These studies provide novel insight into the role of miRNAs in mediating TH regulation of gene expression. Agilent two-color microarray were used to perform gene expression profile in euthyroid and hypothyroid male mouse livers, 5 biological replicates. TLDA (Taqman microRNA Array) was used to explore the miRNA expression profile in euthyroid and hypothyroid male mouse livers, 4 biological replicates.
2010-08-20 | E-GEOD-21277 | biostudies-arrayexpress
Project description:Striatum in rich in GABAergic neurons which require thyroid hormone for their maturation. We used propyl thio uracyl to make mice hypothyroid, and then restored the hormonal level using thyroid hormone. This provided 3 groups of mice for striatum RNAseq analysis. Our results point to GABAergic neurons as direct targets of thyroid hormone during brain development and suggest that many defects seen in hypothyroid brains may be secondary to GABAergic neuron malfunction.
2020-01-31 | GSE144071 | GEO
Project description:MicroRNAs (miRNAs) are extensively in diverse biological processes. However, very little is known about the role of miRNAs in mediating thyroid hormones (TH) action. Maintenance of appropriate TH levels is known to be critically important for development, differentiation and maintenance of metabolic balance in mammals. We induced transient hypothyroidism in juvenile mice by short term exposure to methimazole and perchlorate from post natal day (PND) 12 to 15. The expression of miRNAs in the liver was analyzed with the Taqman Low Density Array (containing up to 600 rodent microRNAs). We found the expression of 40 miRNAs was significantly altered in the liver of hypothyroid mice compared to euthyroid controls. Among the miRNAs, miR-1/206/133 exhibited a massive increase in expression (50 – 500 folds). To further explore TH effect on miR-1/206/133, we treated mouse hepatocyte AML 12 cells with 10 nm T3 for 1 hr and 24 hrs. TH treatment induced the down-regulation of miR-1/206/133b at both time points, reaching statistical significance at 24 hrs. To identify the genes targeted by these miRNAs, DNA microarrays were used to examine hepatic mRNA levels in the hypothyroid mouse model alongside controls. We found transcripts from 92 known genes were significantly altered in hypothyroid mice. Web-based target predication softwares (TargetScan and Microcosm) identified 14 of these transcripts as targets of miR-1/106/133. The vast majority of these mRNA targets were significantly down-regulated in hypothyroid mice, corresponding well with the up-regulation of miR-1/206/133 in hypothyroid mouse liver. The results suggest that TH regulation of these genes may occur secondarily via the reduced repression consequent to TH-induced down-regulation of miR-1/206/133. These studies provide novel insight into the role of miRNAs in mediating TH regulation of gene expression.
2010-08-20 | GSE21277 | 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. 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: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:Purpose: The objective of this study was to determine the cardiac gene expression prifile in the whole heart of mice with mutated thyroid receptor alpha 1 (TRα1R384C+/m) in control condition as well as after treatement with 3,3´,5-triiodo-L-thyronine (T3) for 12 days.
2023-04-23 | GSE206337 | GEO