Do unliganded thyroid hormone receptors have physiological functions?

Chassande, Olivier

doi:10.1677/jme.0.0310009

Cited by 55 publications

(44 citation statements)

References 63 publications

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“…T3 derived from D2 activity in skeletal muscle may also contribute to circulating levels of T3. Conversely, D3 catalyzes the irreversible 5-deiodination of T4 and T3 to the inactive metabolites rT3 (3,5,5'-T3, or reverse T3) and 3,3'-T2, thereby protecting target cells from excess of THs, that can be deleterious especially during embryogenesis (Chassande, 2003). Thus, TH uptake and metabolism determine the levels of T3 availability into the cells.…”

Section: -Introductionmentioning

confidence: 99%

Thyroid hormones and the control of cell proliferation or cell differentiation: Paradox or duality?

Kress

Samarut

Plateroti

2009

Molecular and Cellular Endocrinology

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Thyroid hormones and the control of cell proliferation or cell differentiation: paradox or duality?. Molecular and Cellular Endocrinology, Elsevier, 2009, 313 (1-2) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. SummaryAmphibian metamorphosis perfectly illustrates a key paradox: thyroid hormones control diverse cellular processes depending on the tissue context. This point is also reinforced by a recent accumulation of evidence. For example, thyroid hormones and their nuclear receptor TRs have been described to function in different systems in synergy and/or in antagonism with other signaling pathways. This interaction helps explain their pleiotropic roles. This review summarizes the most important advances in this field, focusing in particular on the key action of thyroid hormones in controlling the balance between the processes of cell proliferation and cell differentiation in a few organs, with special attention paid to the intestine. We highlight similarities between the cellular and molecular events occurring during postnatal intestinal maturation at metamorphosis in amphibians, and comparable events observed at weaning in mice. 1-Introduction1.1 Thyroid hormone production Thyroid hormones (THs), L-thyroxine or T4 and 3,5,3'-L-triiodothyronine or T3, are essential for the development of several organs, including the central nervous system, skeleton, heart, intestine, skeletal muscle and sensory organs. Moreover, they also have important regulatory effects on oxygen consumption and metabolic rate (Oppenheimer et al., 1987). The follicular cells of the thyroid gland synthesize and secrete both hormones, but T4 is the most abundant. This process is under the control of circulating THs levels through the hypothalamuspituitary-thyroid feedback regulatory loop (rev. in Fredric and Wondisford, 2004). The intracellular concentration of T3 is dependent upon the uptake of T3 and T4, and their subsequent metabolism (Bianco and Kim, 2006). In fact, both hormones are actively transported across the cell membrane by specific transporter proteins, of which monocarboxylate transporter-8 is the best characterized (Dumitrescu et al., 2004;Friesema et al., 2004; rev. in Refetoff andDumitrescu, 2007 andVisser et al., 2007). Three iodothyronine deiodinase selenoenzymes (D1, D2 and D3) regulate TH activation and catabolism (Bianco and Kim, 2006). D1 and D2 catalyze the 5'-deiodination of T4 to its active metabolite T3. T3 is generated from the activity of D1, which is the main source of circulating T3. In contrast, D2 is the isoenzyme primarily responsible for local production of T3 in target cells. T3 derived from ...

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Section: -Introductionmentioning

confidence: 99%

Thyroid hormones and the control of cell proliferation or cell differentiation: Paradox or duality?

Kress

Samarut

Plateroti

2009

Molecular and Cellular Endocrinology

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“…In the absence of TH, the unliganded receptors (apo-receptors) recruit co-repressors and repress the transcription of target genes. Upon hormone binding, the receptors (holo-receptors) exchange co-repressors for co-activators and activate transcription (6). TRa1 is the predominant TR isoform in the heart and plays an important role in determining cardiac function (7,8).…”

Section: Introductionmentioning

confidence: 99%

Time-dependent changes in the expression of thyroid hormone receptor α1 in the myocardium after acute myocardial infarction: possible implications in cardiac remodelling

et al. 2007

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The present study investigated whether changes in thyroid hormone (TH) signalling can occur after acute myocardial infarction (AMI) with possible physiological consequences on myocardial performance. TH may regulate several genes encoding important structural and regulatory proteins particularly through the TRa1 receptor which is predominant in the myocardium. AMI was induced in rats by ligating the left coronary artery while sham-operated animals served as controls. This resulted in impaired cardiac function in AMI animals after 2 and 13 weeks accompanied by a shift in myosin isoforms expression towards a fetal phenotype in the non-infarcted area. Cardiac hypertrophy was evident in AMI hearts after 13 weeks but not at 2 weeks. This response was associated with a differential pattern of TH changes at 2 and 13 weeks; T 3 and T 4 levels in plasma were not changed at 2 weeks but T 3 was significantly lower and T 4 remained unchanged at 13 weeks. A twofold increase in TRa1 expression was observed after 13 weeks in the non-infarcted area, P!0.05 versus sham operated, while TRa1 expression remained unchanged at 2 weeks. A 2.2-fold decrease in TRb1 expression was found in the non-infarcted area at 13 weeks, P!0.05, while no change in TRb1 expression was seen at 2 weeks. Parallel studies with neonatal cardiomyocytes showed that phenylephrine (PE) administration resulted in 4.5-fold increase in the expression of TRa1 and 1.6-fold decrease in TRb1 expression versus untreated, P!0.05. In conclusion, cardiac dysfunction which occurs at late stages after AMI is associated with increased expression of TRa1 receptor and lower circulating tri-iodothyronine levels. Thus, apo-TRa1 receptor state may prevail contributing to cardiac fetal phenotype. Furthermore, down-regulation of TRb1 also contributes to fetal phenotypic changes. a1-adrenergic signalling is, at least in part, involved in this response. 156 415-424 European Journal of Endocrinology

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“…The TRa and TRb genes generate, via alternative splicing, four thyroid hormone-binding receptors, namely TRa 1 and TRb 1-3 (Williams 2000, Chassande 2003). In addition, several proteins, including TRa 2 , which do not bind thyroid hormone-response elements and/or thyroid hormones, are formed.…”

Section: Introductionmentioning

confidence: 99%

Expression of thyroid hormone receptors A and B in developing rat tissues; evidence for extensive posttranscriptional regulation

Keijzer

Blommaart²,

Labruyère³

et al. 2007

Journal of Molecular Endocrinology

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The perinatal changes in the pattern of expression of the thyroid hormone receptor (TR) isoforms TRa 1 TRa 2 , TRb 1 , and TRb 2 were investigated using in situ hybridization and immunohistochemistry, and RT-PCR and western blotting as visualization and quantification techniques respectively. In liver, lung, and kidney, TRa mRNA was expressed in the stromal and TRb mRNA in the parenchymal component of the tissues. When compared with liver, TRa mRNA concentrations were tenfold higher in lung, kidney, and intestine, and 100-fold higher in brain, with TRa 2 mRNA concentrations exceeding those of TRa 1 5-to 10-fold. Tissue TRb 1 mRNA concentrations were similar in liver, lung, and brain, and 3-to 5-fold higher in kidney and intestine. None of the TRb 2 mRNA could be detected outside the pituitary. Tissue TRa 2 and TRb 1 protein levels reached adult levels at 5 days before birth, whereas TRa 1 protein peaked after birth. Because of the distinct time-course of thyroid hormonebinding receptors TRa 1 and TRb 1 , we speculate that an initiating, TRb 1 -mediated signaling from the parenchyma is followed by a TRa 1 -mediated response in the stroma. When compared with organs with a complementary parenchymal-stromal expression pattern, organs with extensive cellular co-expression of TRa and TRb (brain and intestinal epithelium) were characterized by a very low TRa protein: mRNA ratio, implying a low translational efficiency of TR mRNA or a high turnover of TR protein. The data indicate that the TR-dependent regulatory cascades are controlled differently in organs with a complementary tissue expression pattern and in those with cellular co-expression of the TRa and TRb genes.

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Do unliganded thyroid hormone receptors have physiological functions?

Cited by 55 publications

References 63 publications

Thyroid hormones and the control of cell proliferation or cell differentiation: Paradox or duality?

Thyroid hormones and the control of cell proliferation or cell differentiation: Paradox or duality?

Time-dependent changes in the expression of thyroid hormone receptor α1 in the myocardium after acute myocardial infarction: possible implications in cardiac remodelling

Expression of thyroid hormone receptors A and B in developing rat tissues; evidence for extensive posttranscriptional regulation

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