Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA996036 | ENA |
REPOSITORIES: ENA
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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: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:Hypothyroidism is a prevalent endocrine disorder that is characterized by the insufficient production of thyroid hormones (T3/T4), with etiologies related to environmental, autoimmune factors, or genetic variants. Thyroglobulin (Tg) serves as the prohormone to T3/T4 production and due to a large genetic diversity there are many variants of clinical uncertainty. Here, we leveraged the large-scale “All of Us” biobank to investigate disease association of Tg variants that are more prevalent in the general population compared to previously characterized variants. We compared these variants to thyroid stimulating hormone levels and levothyroxine (LT4) usage to estimate thyroid function. This identified R152H, Q870H, A993T, P1012L and P1494L variants linked to an increased susceptibility to levothyroxine usage and decreased thyroid function while the R320C variant was associated with a decrease in thyroid function. Molecular characterization and secretion of these variants in Fisher rat thyroid cells showed decreased secretion efficiency and/or correlates with higher anti-TPO antibody levels in participants for disease associated variants while benign variants showed minimal effect. Using previously determined structures of Tg, variants found with a decrease in thyroid efficiency are in structural positions that disrupt stabilizing bonds, but variants with minimal effect are in more flexible regions with fewer interactions. Affinity purification mass spectrometry demonstrated that secretion deficient variants show higher engagement with the protein homeostasis network. We estimate that around 150,000 individuals in the US could benefit from precision medicine with the variants highlighted in this study currently take levothyroxine, with ~100,000 of those individuals carrying the Q870H variant. Our findings highlight the power of combining data from large public biobanks with molecular characterization to better understand the genotype to phenotype relationships of Tg. Our analysis suggests that Q870H serves as a possible candidate to be targeted by molecular therapies to restore secretion and T3/T4 production offering a precision medicine approach beyond LT4 replacement therapy.
2026-08-07 | PXD069688 | Pride
Project description:We investigated the effects of thyroid hormone disruptions on gene expression in juvenile mice liver to develop a stronger understanding of the mechanisms by which thyroid disrupting chemicals impair development. Gene expression was examined by hybridization of hepatic RNA to Agilent mouse microarrays for hyper-, hypo-, hypo-replacement (hypo+) and euthyroid animals. Keywords: Toxicogenomics, biomarkers of thyroid disruptors Hypothyroidism was induced from post natal day (PND) 13 to 15 by adding model thyroid toxicants methimazole and sodium perchlorate to drinking water of pregnant females. Hyperthyroidism was induced by intraperitoneal injections (i.p.) of THs at PND 15, 4 hours before decapitation and tissue collection. For the hypothyroid/replacement group; dams were provided with drinking water for 3 days (PND 13 to 15), containing a mixture of methimazole/sodium perchlorate. Pups then received intraperitoneal injections of thyoid hormones on PND 15, 4 hours before decapitation and tissue collection.
2012-03-29 | E-GEOD-21307 | biostudies-arrayexpress
Project description:We ablated the expression of the Nuclear Receptor Corepressor 1 specifically in mice livers and rendered them hypothyroid. Then we performed H3K27 acetylation CHIP-Seq. We found decreased H3K27ac in the livers of hypothyroid wild type and NCoR1KO mice. Therefore, we concluded that the thyroid hormone receptor may recruit histone deacetilases independently of NCoR1.
2017-09-18 | GSE99475 | GEO
Project description:The function of the thyroid gland is to metabolize iodide to synthesize hormones that act on almost all tissues and are essential for normal growth and metabolism. Low plasma levels of thyroid hormones lead to hypothyroidism, which is one of the most common diseases in the general population and cannot be always satisfactorily treated by lifelong hormone replacement. Therefore, in addition to the lack of in vitro tractable models to study human thyroid development, differentiation and maturation, there is a need for new therapeutic approaches that involve replacement of thyroid tissue to better control hormone balance. Here we report the first model of thyroid organoids derived from human embryonic stem cells that produce thyroid hormones in vitro and are capable of restoring plasma thyroid hormone levels when transplanted into athyreotic mice.
2022-10-24 | GSE181256 | GEO
Project description:The function of the thyroid gland is to metabolize iodide to synthesize hormones that act on almost all tissues and are essential for normal growth and metabolism. Low plasma levels of thyroid hormones lead to hypothyroidism, which is one of the most common diseases in the general population and cannot be always satisfactorily treated by lifelong hormone replacement. Therefore, in addition to the lack of in vitro tractable models to study human thyroid development, differentiation and maturation, there is a need for new therapeutic approaches that involve replacement of thyroid tissue to better control hormone balance. Here we report the first model of thyroid organoids derived from human embryonic stem cells that produce thyroid hormones in vitro and are capable of restoring plasma thyroid hormone levels when transplanted into athyreotic mice.
2022-10-24 | GSE203084 | GEO
Project description:The function of the thyroid gland is to metabolize iodide to synthesize hormones that act on almost all tissues and are essential for normal growth and metabolism. Low plasma levels of thyroid hormones lead to hypothyroidism, which is one of the most common diseases in the general population and cannot be always satisfactorily treated by lifelong hormone replacement. Therefore, in addition to the lack of in vitro tractable models to study human thyroid development, differentiation and maturation, there is a need for new therapeutic approaches that involve replacement of thyroid tissue to better control hormone balance. Here we report the first model of thyroid organoids derived from human embryonic stem cells that produce thyroid hormones in vitro and are capable of restoring plasma thyroid hormone levels when transplanted into athyreotic mice.
2022-10-24 | GSE181452 | GEO
Project description:The function of the thyroid gland is to metabolize iodide to synthesize hormones that act on almost all tissues and are essential for normal growth and metabolism. Low plasma levels of thyroid hormones lead to hypothyroidism, which is one of the most common diseases in the general population and cannot be always satisfactorily treated by lifelong hormone replacement. Therefore, in addition to the lack of in vitro tractable models to study human thyroid development, differentiation and maturation, there is a need for new therapeutic approaches that involve replacement of thyroid tissue to better control hormone balance. Here we report the first model of thyroid organoids derived from human embryonic stem cells that produce thyroid hormones in vitro and are capable of restoring plasma thyroid hormone levels when transplanted into athyreotic mice.
2022-10-24 | GSE201558 | GEO
Project description:We used microarrays to investigate differential gene expression in different thyroid hormone receptor beta mouse models. Hypothyroid wild type, TRbeta KO and TRbeta GS mutant mice were treated with T3 or vehicle alone. Microarray analysis revealed that the gene expression pattern in TRbeta GS mutant mice was similar to that in TRbeta KO mice.
2018-02-01 | GSE93864 | GEO