scholarly journals Empowering thyroid hormone research in human subjects using OMICs technologies

2018 ◽  
Vol 238 (1) ◽  
pp. R13-R29 ◽  
Author(s):  
Maik Pietzner ◽  
Tim Kacprowski ◽  
Nele Friedrich
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Target Genes ◽  
Human Subjects ◽  
Experimental Studies ◽  
Analytical Techniques ◽  
Population Based ◽  
Whole Body ◽  
Hormone Research ◽  
Whole Body Metabolism

OMICs subsume different physiological layers including the genome, transcriptome, proteome and metabolome. Recent advances in analytical techniques allow for the exhaustive determination of biomolecules in all OMICs levels from less invasive human specimens such as blood and urine. Investigating OMICs in deeply characterized population-based or experimental studies has led to seminal improvement of our understanding of genetic determinants of thyroid function, identified putative thyroid hormone target genes and thyroid hormone-induced shifts in the plasma protein and metabolite content. Consequently, plasma biomolecules have been suggested as surrogates of tissue-specific action of thyroid hormones. This review provides a brief introduction to OMICs in thyroid research with a particular focus on metabolomics studies in humans elucidating the important role of thyroid hormones for whole body metabolism in adults.

scholarly journals Thyroid Hormone Action in Cerebellum and Cerebral Cortex Development

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Fabrice Chatonnet ◽  
Frédéric Picou ◽  
Teddy Fauquier ◽  
Frédéric Flamant
Keyword(s):  
Cerebral Cortex ◽  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Glial Cell ◽  
Nuclear Receptors ◽  
Target Genes ◽  
Cell Types ◽  
Hormone Action ◽  
Cerebral Cortex Development ◽  
Thyroid Hormone Action

Thyroid hormones (TH, including the prohormone thyroxine (T4) and its active deiodinated derivative 3,,5-triiodo-L-thyronine (T3)) are important regulators of vertebrates neurodevelopment. Specific transporters and deiodinases are required to ensure T3 access to the developing brain. T3 activates a number of differentiation processes in neuronal and glial cell types by binding to nuclear receptors, acting directly on transcription. Only few T3 target genes are currently known. Deeper investigations are urgently needed, considering that some chemicals present in food are believed to interfere with T3 signaling with putative neurotoxic consequences.

Respiratory adaptation to hyperthyroidism

1960 ◽  
Vol 15 (6) ◽  
pp. 1107-1112 ◽  
Author(s):  
H. Valtin ◽  
S. M. Tenney
Keyword(s):  
Ventilatory Response ◽  
Human Subjects ◽  
Respiratory Center ◽  
Whole Body ◽  
Response Curves ◽  
Direct Stimulation ◽  
Enhanced Sensitivity ◽  
Whole Body Metabolism ◽  
Sensitivity Changes ◽  
Respiratory Stimulation

In order to test the general postulate that increases in whole body metabolism are accompanied by net respiratory stimulation, respiratory adaptation to thyrotoxicosis was studied in clinical hyperthyroidism and in experimental hyperthyroidism in man and the rat. It was found that in contrast to other hypermetabolic states such as fever and salicylate and dinitrophenol administration, alveolar CO2 tension rises in hyperthyroidism, reflecting a proportionately greater increase in metabolism (CO2 production) than in alveolar ventilation. Ventilatory response curves in three human subjects with experimentally induced hyperthyroidism showed no increase in sensitivity (Deltaa/DeltaPaCOCO2 of the respiratory center to CO2. This finding differs from that in salicylism and dinitrophenol administration in which enhanced sensitivity is manifest. It is concluded that the respiratory stimulation resulting from increased CO2 production is modified by factors such as changes in respiratory center sensitivity, changes in cerebral blood flow and direct stimulation of the respiratory center, so that the net respiratory adjustment cannot be predicted from a knowledge of the increase in metabolism alone. Submitted on April 7, 1960

scholarly journals 3,5-T2 alters murine genes relevant for xenobiotic, steroid, and thyroid hormone metabolism

2016 ◽  
Vol 56 (4) ◽  
pp. 311-323 ◽  
Author(s):  
Julika Lietzow ◽  
Janine Golchert ◽  
Georg Homuth ◽  
Uwe Völker ◽  
Wenke Jonas ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Phase Iii ◽  
Whole Body ◽  
High Dose ◽  
Thyroid Hormone Metabolism ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Novel Target

The endogenous thyroid hormone (TH) metabolite 3,5-diiodo-l-thyronine (3,5-T2) acts as a metabolically active substance affecting whole-body energy metabolism and hepatic lipid handling in a desirable manner. Considering possible adverse effects regarding thyromimetic action of 3,5-T2 treatment in rodents, the current literature remains largely controversial. To obtain further insights into molecular mechanisms and to identify novel target genes of 3,5-T2 in liver, we performed a microarray-based liver tissue transcriptome analysis of male lean and diet-induced obese euthyroid mice treated for 4 weeks with a dose of 2.5 µg/g bw 3,5-T2. Our results revealed that 3,5-T2 modulates the expression of genes encoding Phase I and Phase II enzymes as well as Phase III transporters, which play central roles in metabolism and detoxification of xenobiotics. Additionally, 3,5-T2 changes the expression of TH responsive genes, suggesting a thyromimetic action of 3,5-T2 in mouse liver. Interestingly, 3,5-T2 in obese but not in lean mice influences the expression of genes relevant for cholesterol and steroid biosynthesis, suggesting a novel role of 3,5-T2 in steroid metabolism of obese mice. We concluded that treatment with 3,5-T2 in lean and diet-induced obese male mice alters the expression of genes encoding hepatic xenobiotic-metabolizing enzymes that play a substantial role in catabolism and inactivation of xenobiotics and TH and are also involved in hepatic steroid and lipid metabolism. The administration of this high dose of 3,5-T2 might exert adverse hepatic effects. Accordingly, the conceivable use of 3,5-T2 as pharmacological hypolipidemic agent should be considered with caution.

Prospects for the use of thyroid hormones in patients with heart failure

2021 ◽  
Author(s):  
S. M. Pyvоvar ◽  
Yu. S. Rudyk ◽  
О. B. Krоtоva ◽  
L. V. Panina
Keyword(s):  
Heart Failure ◽  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Animal Studies ◽  
Cardiac Tissue ◽  
Contractile Function ◽  
Heart Function ◽  
Experimental Studies ◽  
Tissue Level ◽  
Free Triiodothyronine

Thyroid hormone therapy in the setting of heart failure is still an «open book» today. There are several unanswered questions: the regimen, doses and schedule of the use of thyroid hormones, the consequences of such therapy. At the same time, the presence of a comorbid pathology of the thyroid gland, which requires the appointment of levothyroxine, allows one to partially answer these questions. Thyroid hormones affect the diastolic and systolic functions of the myocardium. Ventricular contractile function is also affected by changes in hemodynamic conditions secondary to thyroid hormones and peripheral vascular tone. Thyroid hormone homeostasis maintains a positive ventricular-arterial ratio, resulting in a favorable balance for heart function. Experimental studies in rats have shown that chronic hypothyroidism alone can eventually lead to heart failure. Other studies suggest a decrease in the level of free triiodothyronine in the myocardium after myocardial infarction or with arterial hypertension due to the activation of type 3 deiodinase, which leads to deactivation of triiodothyronine and thyroxine. To address these issues, the researchers propose conducting multicenter, randomized, placebo-controlled trials to evaluate the effects of thyroxine replacement in patients with chronic heart failure. The review highlights the growing body of evidence from animal studies and small clinical trials that suggests that low thyroid activity at the cardiac tissue level can negatively affect the progression of heart failure and that treatment with thyroid hormones can lead to an improved prognosis.

scholarly journals Estrogen: An Emerging Regulator of Insulin Action and Mitochondrial Function

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Anisha A. Gupte ◽  
Henry J. Pownall ◽  
Dale J. Hamilton
Keyword(s):  
Estrogen Receptor ◽  
Insulin Action ◽  
Animal Studies ◽  
Experimental Studies ◽  
Fat Distribution ◽  
Metabolic Effects ◽  
Whole Body ◽  
Current State ◽  
Rapid Changes ◽  
Whole Body Metabolism

Clinical trials and animal studies have revealed that loss of circulating estrogen induces rapid changes in whole body metabolism, fat distribution, and insulin action. The metabolic effects of estrogen are mediated primarily by its receptor, estrogen receptor-α; however, the detailed understanding of its mechanisms is incomplete. Recent investigations suggest that estrogen receptor-αelicits the metabolic effects of estrogen by genomic, nongenomic, and mitochondrial mechanisms that regulate insulin signaling, substrate oxidation, and energetics. This paper reviews clinical and experimental studies on the mechanisms of estrogen and the current state of knowledge regarding physiological and pathobiological influences of estrogen on metabolism.

scholarly journals Thyroid hormones inhibit TGF-β signaling and attenuate fibrotic responses

2016 ◽  
Vol 113 (24) ◽  
pp. E3451-E3460 ◽  
Author(s):  
Elvira Alonso-Merino ◽  
Rosa Martín Orozco ◽  
Lidia Ruíz-Llorente ◽  
Olaia A. Martínez-Iglesias ◽  
Juan Pedro Velasco-Martín ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Transcriptional Activation ◽  
Hormone Receptors ◽  
Target Genes ◽  
Direct Interaction ◽  
Beneficial Effects ◽  
Hormone Administration ◽  
Fibrotic Diseases

TGF-β, the most potent profibrogenic factor, acts by activating SMAD (mothers against decapentaplegic) transcription factors, which bind to SMAD-binding elements in target genes. Here, we show that the thyroid hormone triiodothyronine (T3), through binding to its nuclear receptors (TRs), is able to antagonize transcriptional activation by TGF-β/SMAD. This antagonism involves reduced phosphorylation of SMADs and a direct interaction of the receptors with SMAD3 and SMAD4 that is independent of T3-mediated transcriptional activity but requires residues in the receptor DNA binding domain. T3 reduces occupancy of SMAD-binding elements in response to TGF-β, reducing histone acetylation and inhibiting transcription. In agreement with this transcriptional cross-talk, T3 is able to antagonize fibrotic processes in vivo. Liver fibrosis induced by carbon tetrachloride is attenuated by thyroid hormone administration to mice, whereas aged TR knockout mice spontaneously accumulate collagen. Furthermore, skin fibrosis induced by bleomycin administration is also reduced by the thyroid hormones. These findings define an important function of the thyroid hormone receptors and suggest TR ligands could have beneficial effects to block the progression of fibrotic diseases.

scholarly journals Novel uses of thyroid hormones in cardiovascular conditions

Endocrine ◽  
2019 ◽  
Vol 66 (1) ◽  
pp. 115-123 ◽  
Author(s):  
Salman Razvi
Keyword(s):  
Cardiovascular Diseases ◽  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Hormone Therapy ◽  
Large Scale ◽  
Experimental Studies ◽  
Hormone Treatment ◽  
Limited Data ◽  
Hormone Levels ◽  
Thyroid Hormone Levels

Abstract Thyroid hormone levels are reduced in cardiovascular diseases and this phenomenon is associated with worse outcomes. It is unclear whether the changes in thyroid hormone bioavailability to the affected myocardium are beneficial or if this is a maladaptive response. Experimental studies from animal models of acute myocardial infarction (AMI) suggest that thyroid hormone treatment may be beneficial. There is limited data available on the use of thyroid hormones in patients with AMI and heart failure and this suggests that treatment to normalise thyroid hormone levels may be safe and potentially efficacious. Similarly, evidence of thyroid hormone therapy in patients undergoing cardiac surgery or during cardiac transplantation is limited. It is therefore difficult to draw any firm conclusions about benefits or risks of thyroid hormone treatment in these conditions. Large scale clinical trials of thyroid hormones in patients with cardiac conditions are required to confirm safety and evaluate efficacy. Furthermore, it needs to be elucidated which hormone to administer (thyroxine or triiodothyronine), when in the disease pathway to treat, dose of thyroid hormone to administer, and which parameters to utilise to assess safety and efficacy. Until these important questions are answered thyroid hormone therapy in cardiovascular diseases must remain within the research domain.

scholarly journals New Approaches to Thyroid Hormones and Purinergic Signaling

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Gabriel Fernandes Silveira ◽  
Andréia Buffon ◽  
Alessandra Nejar Bruno
Keyword(s):  
Cell Proliferation ◽  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Neurotransmitter Release ◽  
Hormone Receptors ◽  
Target Genes ◽  
Purinergic Signaling ◽  
Thyroid Hormone Receptors ◽  
New Information ◽  
The Relationship

It is known that thyroid hormones influence a wide variety of events at the molecular, cellular, and functional levels. Thyroid hormones (TH) play pivotal roles in growth, cell proliferation, differentiation, apoptosis, development, and metabolic homeostasis via thyroid hormone receptors (TRs) by controlling the expression of TR target genes. Most of these effects result in pathological and physiological events and are already well described in the literature. Even so, many recent studies have been devoted to bringing new information on problems in controlling the synthesis and release of these hormones and to elucidating mechanisms of the action of these hormones unconventionally. The purinergic system was recently linked to thyroid diseases, including enzymes, receptors, and enzyme products related to neurotransmitter release, nociception, behavior, and other vascular systems. Thus, throughout this text we intend to relate the relationship between the TH in physiological and pathological situations with the purinergic signaling.

scholarly journals Circulatory MicroRNAs in Plasma and Atrial Fibrillation in the General Population: The Rotterdam Study

Genes ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 11
Author(s):  
Sven Geurts ◽  
Michelle M. J. Mens ◽  
Maxime M. Bos ◽  
M. Arfan Ikram ◽  
Mohsen Ghanbari ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Plasma Levels ◽  
Target Genes ◽  
Cardiac Fibrosis ◽  
Experimental Studies ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
P Value ◽  
Rotterdam Study ◽  
The Relationship

Background: MicroRNAs (miRNAs), small non-coding RNAs regulating gene expression, have been shown to play an important role in cardiovascular disease. However, limited population-based data regarding the relationship between circulatory miRNAs in plasma and atrial fibrillation (AF) exist. Moreover, it remains unclear if the relationship differs by sex. We therefore aimed to determine the (sex-specific) association between plasma circulatory miRNAs and AF at the population level. Methods: Plasma levels of miRNAs were measured using a targeted next-generation sequencing method in 1999 participants from the population-based Rotterdam Study. Logistic regression and Cox proportional hazards models were used to assess the associations of 591 well-expressed miRNAs with the prevalence and incidence of AF. Models were adjusted for cardiovascular risk factors. We further examined the link between predicted target genes of the identified miRNAs. Results: The mean age was 71.7 years (57.1% women), 98 participants (58 men and 40 women) had prevalent AF at baseline. Moreover, 196 participants (96 men and 100 women) developed AF during a median follow-up of 9.0 years. After adjusting for multiple testing, miR-4798-3p was significantly associated with the odds of prevalent AF among men (odds ratio, 95% confidence interval, 0.39, 0.24–0.66, p-value = 0.000248). No miRNAs were significantly associated with incident AF. MiR-4798-3p could potentially regulate the expression of a number of AF-related genes, including genes involved in calcium and potassium handling in myocytes, protection of cells against oxidative stress, and cardiac fibrosis. Conclusions: Plasma levels of miR-4798-3p were significantly associated with the odds of prevalent AF among men. Several target genes in relation to AF pathophysiology could potentially be regulated by miR-4798-3p that warrant further investigations in future experimental studies.

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