Differential transcriptome regulation by 3,5-T2 and 3',3,5-T3 in brain and liver uncovers novel roles for thyroid hormones in tilapia.
Ontology highlight
ABSTRACT:
SUBMITTER: Olvera A
PROVIDER: S-EPMC5678081 | biostudies-literature | 2017 Nov
REPOSITORIES: biostudies-literature
Publications
Differential transcriptome regulation by 3,5-T2 and 3',3,5-T3 in brain and liver uncovers novel roles for thyroid hormones in tilapia.
Olvera A A Martyniuk C J CJ Buisine N N Jiménez-Jacinto V V Sanchez-Flores A A Sachs L M LM Orozco A A
Scientific reports 20171108 1
Although 3,5,3'-triiodothyronine (T3) is considered to be the primary bioactive thyroid hormone (TH) due to its high affinity for TH nuclear receptors (TRs), new data suggest that 3,5-diiodothyronine (T2) can also regulate transcriptional networks. To determine the functional relevance of these bioactive THs, RNA-seq analysis was conducted in the cerebellum, thalamus-pituitary and liver of tilapia treated with equimolar doses of T2 or T3. We identified a total of 169, 154 and 2863 genes that wer ...[more]
Similar Datasets
Project description:We used a RNA-seq approach to determine the effect of 3,5-di-iodothyronine (T2) and 3,5,3'-tri-iodothyronine (T3) exogenous treatment on the transcriptome of tilapia (Oreochromis niloticus) liver, cerebellum, and thalamus-pituitary. We identified a total of 169, 154 and 2863 genes that were Thyroid hormone-regulated (FDR < 0.05) in tilapia cerebellum, thalamus-pituitary and liver, respectively. Among those, 130, 96 and 349 genes were uniquely regulated by T3, whereas 22, 40 and 929 were only regulated by T2 in the cerebellum, thalamus-pituitary and liver.
2017-04-10 | GSE96046 | GEO
Project description:In contrast to mammalian adults, myelination in teleosts occurs throughout their lifespan and most of the progenitor cells are originated in the cerebellum. To understand the role that thyroid hormones (THs) play in juvenile cerebellar myelination in teleosts, we identified and localised the expression of genes involved in TH signalling (mct8, oatp1c1, dio2, dio3, thraa and l-thrb1) and analysed the effects of the two bioactive THs, T2 and T3, upon their regulation, as well as upon some structural components of the myelination process. Ex vivo approaches using organotypic cerebellar cultures followed by FISH and qPCR showed gene-specific localisation and regulation of TH signalling genes in the cerebellar nuclei. In vivo approaches using methimazole (MMI)-treated juvenile tilapias replaced with low doses of T3 and T2 showed by immunofluorescence that myelin fibres in the cerebellum are more abundant in the granular layer and that their visible size is reduced after MMI treatment but partially restored with TH replacement, suggesting that low doses of TH promote the re-myelination process in an altered condition. Together, our data support the idea that T2 and T3 promote myelination via different pathways and prompt T2 as a target for further analysis as a promising therapy for hypomyelination.
| S-EPMC6517622 | biostudies-literature
Project description:Over the last decades, thyroid hormone metabolites (THMs) received marked attention as it has been demonstrated that they are bioactive compounds. Their concentrations were determined by immunoassay or mass-spectrometry methods. Among those metabolites, 3,5-diiodothyronine (3,5-T2), occurs at low nanomolar concentrations in human serum, but might reach tissue concentrations similar to those of T4 and T3, at least based on data from rodent models. However, the immunoassay-based measurements in human sera revealed remarkable variations depending on antibodies used in the assays and thus need to be interpreted with caution. In clinical experimental approaches in euthyroid volunteers and hypothyroid patients using the immunoassay as the analytical tool no evidence of formation of 3,5-T2 from its putative precursors T4 or T3 was found, nor was any support found for the assumption that 3,5-T2 might represent a direct precursor for serum 3-T1-AM generated by combined deiodination and decarboxylation from 3,5-T2, as previously documented for mouse intestinal mucosa. We hypothesized that lowered endogenous production of 3,5-T2 in patients requiring T4 replacement therapy after thyroidectomy or for treatment of autoimmune thyroid disease, compared to production of 3,5-T2 in individuals with intact thyroid glands might contribute to the discontent seen in a subset of patients with this therapeutic regimen. So far, our observations do not support this assumption. However, the unexpected association between high serum 3,5-T2 and elevated urinary concentrations of metabolites related to coffee consumption requires further studies for an explanation. Elevated 3,5-T2 serum concentrations were found in several situations including impaired renal function, chronic dialysis, sepsis, non-survival in the ICU as well as post-operative atrial fibrillation (POAF) in studies using a monoclonal antibody-based chemoluminescence immunoassay. Pilot analysis of human sera using LC-linear-ion-trap-mass-spectrometry yielded 3,5-T2 concentrations below the limit of quantification in the majority of cases, thus the divergent results of both methods need to be reconciliated by further studies. Although positive anti-steatotic effects have been observed in rodent models, use of 3,5-T2 as a muscle anabolic, slimming or fitness drug, easily obtained without medical prescription, must be advised against, considering its potency in suppressing the HPT axis and causing adverse cardiac side effects. 3,5-T2 escapes regular detection by commercially available clinical routine assays used for thyroid function tests, which may be seriously disrupted in individuals self-administering 3,5-T2 obtained over-the counter or from other sources.
| S-EPMC6960127 | biostudies-literature
Project description:In general, 3,5-diiodothyronine (3,5-T2) increases the resting metabolic rate and oxygen consumption, exerting short-term beneficial metabolic effects on rats subjected to a high-fat diet. Our aim was to evaluate the effects of chronic 3,5-T2 administration on the hypothalamus-pituitary-thyroid axis, body mass gain, adipose tissue mass, and body oxygen consumption in Wistar rats from 3 to 6 months of age. The rats were treated daily with 3,5-T2 (25, 50, or 75??g/100?g body weight, s.c.) for 90 days between the ages of 3 and 6 months. The administration of 3,5-T2 suppressed thyroid function, reducing not only thyroid iodide uptake but also thyroperoxidase, NADPH oxidase 4 (NOX4), and thyroid type 1 iodothyronine deiodinase (D1 (DIO1)) activities and expression levels, whereas the expression of the TSH receptor and dual oxidase (DUOX) were increased. Serum TSH, 3,3',5-triiodothyronine, and thyroxine were reduced in a 3,5-T2 dose-dependent manner, whereas oxygen consumption increased in these animals, indicating the direct action of 3,5-T2 on this physiological variable. Type 2 deiodinase activity increased in both the hypothalamus and the pituitary, and D1 activities in the liver and kidney were also increased in groups treated with 3,5-T2. Moreover, after 3 months of 3,5-T2 administration, body mass and retroperitoneal fat pad mass were significantly reduced, whereas the heart rate and mass were unchanged. Thus, 3,5-T2 acts as a direct stimulator of energy expenditure and reduces body mass gain; however, TSH suppression may develop secondary to 3,5-T2 administration.
| S-EPMC4045230 | biostudies-literature
Project description:Nonalcoholic fatty liver disease (NAFLD) is a major health problem worldwide, and is often associated with lipotoxic injury, defective mitochondrial function, and insulin resistance. Thyroid hormones (THs) are important regulators of hepatic lipid metabolism. Among the THs, diiodothyronine (T2) and triiodothyronine (T3) have shown promising results in lowering hepatic fat content in various models of NAFLD. In this study, we used a targeted metabolomics approach to investigate the differential effects of T2 and T3 on the early metabolic adaptation in the livers of rats fed high fat diet (HFD), a period when hepatosteatosis is reversible. Our results showed that both T2 and T3 strongly induced autophagy and intra-hepatic acylcarnitine flux but prevented the generation of sphingolipid/ceramides in animals fed HFD. Interestingly, although both T2 and T3 decreased hepatic fat content, only T2 was able to rescue the impairment in AKT and MAPK/ERK pathways caused by HFD. In summary, we have identified and characterized the effects of T2 and T3 on hepatic metabolism during short-term exposure to HFD. These findings illuminate the common and divergent metabolic pathways by T2 and T3 that also may be important in the prevention and treatment of NAFLD.
| S-EPMC5435676 | biostudies-literature
Project description:Cancer has an important and considerable gender differential susceptibility confirmed by several epidemiological studies. Gastric (GC) and thyroid cancer (TC) are examples of malignancies with a higher incidence in males and females, respectively. Beyond environmental predisposing factors, it is expected that gender-specific gene deregulation contributes to this differential incidence. We performed a detailed characterization of the transcriptomic differences between genders in normal and tumor tissues from stomach and thyroid using Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) data. We found hundreds of sex-biased genes (SBGs). Most of the SBGs shared by normal and tumor belong to sexual chromosomes, while the normal and tumor-specific tend to be found in the autosomes. Expression of several cancer-associated genes is also found to differ between sexes in both types of tissue. Thousands of differentially expressed genes (DEGs) between paired tumor-normal tissues were identified in GC and TC. For both cancers, in the most susceptible gender, the DEGs were mostly under-expressed in the tumor tissue, with an enrichment for tumor-suppressor genes (TSGs). Moreover, we found gene networks preferentially associated to males in GC and to females in TC and correlated with cancer histological subtypes. Our results shed light on the molecular differences and commonalities between genders and provide novel insights in the differential risk underlying these cancers.
| S-EPMC7406663 | biostudies-literature
Project description:Thyroid hormones are biologically active small molecules responsible for growth and development regulation, basal metabolic rate, and lipid and carbohydrate metabolism. Liquid chromatography mass spectrometry (LC-MS) can be used to quantify thyroid hormones blood level with high speed and selectivity, aiming to improve the diagnosis and treatment of the severe pathological conditions in which they are implicated, i.e., hypo- and hyperthyroidism. In this work, the gas-phase behavior of the isomeric thyroid hormones triiodothyronine (T3) and reverse triiodothyronine (rT3) in their deprotonated form was studied at a molecular level using MS-based techniques. Previously reported collision-induced dissociation experiments yielded distinct spectra despite the high structural similarity of the two compounds, suggesting different charge sites to be responsible. Infrared multiple photon dissociation spectroscopy on [T3-H]- and [rT3-H]- was performed, and the results were interpreted using DFT and MP2 calculations, assessing the prevalence of T3 in the carboxylate form and rT3 as a phenolate isomer. The different deprotonation sites of the two isomers were also found to drive their ion-mobility behavior. In fact, [T3-H]- and [rT3-H]- were successfully separated. Drift times were correlated with collisional cross section values of 209 and 215 Å2 for [T3-H]- and [rT3-H]-, respectively. Calculations suggested the charge site to be the main parameter involved in the different mobilities of the two anions. Finally, bare [T3-H]- and [rT3-H]- were made to react with neutral acetylacetone and trifluoroacetic acid, confirming rT3 to be more acidic than T3 in agreement with the calculated gas-phase acidities of T3 and rT3 equal to 1345 and 1326 kJ mol-1, respectively.
| S-EPMC8581966 | biostudies-literature
Project description:Normal thyroid hormone level is essential to maintain the normal physiologic function of the human body. Disturbances of these hormone levels have variable clinical manifestations ranging from asymptomatic to severe illness. Resistance to thyroid hormone (RTH) is a syndrome characterized by reduced intracellular action of T3, the active thyroid hormone. It is a rare autosomal dominant condition and occurs mostly due to heterogeneous mutations in the thyroid hormone receptor. Other causes of RTH include thyroid hormone cell membrane transport defect and thyroid hormone metabolism defect. Affected individuals present with symptoms of both increased and decreased thyroid hormone action, depending on the tissue's predominant receptor isoform expression, the magnitude of hormonal resistance, and the effectiveness of compensatory mechanisms. Here, we share our experience in diagnosing a case of RTH confirmed with a genetic test and found to have sequence variant mutation that is not well described in the literature previously due to the absence of genetic conclusive evidence.
| S-EPMC8184159 | biostudies-literature
Project description:Endometriosis is characterized by the presence of ectopic endometrial cells outside the uterine cavity. Thyroid autoimmunity has been associated with endometriosis. This work investigated the potential pathophysiological link between endometriosis and thyroid disorders. Transcripts and proteins involved in thyroid metabolism are dysregulated in eutopic and ectopic endometrium of endometriotic patients, leading to resistance of ectopic endometrium to triiodothyronine (T3) action and local accumulation of thyroxine (T4). Thyroid-stimulating hormone (TSH) acts as a proliferative and prooxidative hormone on all endometria of endometriosis patients and controls, whereas T3 and T4 act to specifically increase ectopic endometrial cell proliferation and reactive oxygen species (ROS) production. Mouse studies confirmed the data gained in vitro since endometriotic implants were found to be bigger when thyroid hormones increased. A retrospective analysis of endometriosis patients with or without a thyroid disorder revealed an increased chronic pelvic pain and disease score in endometriotic patients with a thyroid disorder.
| S-EPMC6575600 | biostudies-literature
Project description:BACKGROUND: Abiotic stress, including low temperature, limits the productivity and geographical distribution of plants, which has led to significant interest in understanding the complex processes that allow plants to adapt to such stresses. The wide range of physiological, biochemical and molecular changes that occur in plants exposed to low temperature require a robust global approach to studying the response. We have employed Serial Analysis of Gene Expression (SAGE) to uncover changes in the transcriptome of Arabidopsis thaliana over a time course of low temperature stress. RESULTS: Five SAGE libraries were generated from A. thaliana leaf tissue collected at time points ranging from 30 minutes to one week of low temperature treatment (4 degrees C). Over 240,000 high quality SAGE tags, corresponding to 16,629 annotated genes, provided a comprehensive survey of changes in the transcriptome in response to low temperature, from perception of the stress to acquisition of freezing tolerance. Interpretation of these data was facilitated by representing the SAGE data by gene identifier, allowing more robust statistical analysis, cross-platform comparisons and the identification of genes sharing common expression profiles. Simultaneous statistical calculations across all five libraries identified 920 low temperature responsive genes, only 24% of which overlapped with previous global expression analysis performed using microarrays, although similar functional categories were affected. Clustering of the differentially regulated genes facilitated the identification of novel loci correlated with the development of freezing tolerance. Analysis of their promoter sequences revealed subsets of genes that were independent of CBF and ABA regulation and could provide a mechanism for elucidating complementary signalling pathways. The SAGE data emphasised the complexity of the plant response, with alternate pre-mRNA processing events increasing at low temperatures and antisense transcription being repressed. CONCLUSION: Alternate transcript processing appears to play an important role in enhancing the plasticity of the stress induced transcriptome. Novel genes and cis-acting sequences have been identified as compelling targets to allow manipulation of the plant's ability to protect against low temperature stress. The analyses performed provide a contextual framework for the interpretation of quantitative sequence tag based transcriptome analysis which will prevail with the application of next generation sequencing technology.
| S-EPMC2568001 | biostudies-literature