• Journal of Interdisciplinary Genomics
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• v.5 no.2
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• pp.32-34
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• 2023

Resistance to thyroid hormone syndrome (RTH) is a genetic disease caused by the mutation of either the thyroid hormone receptor-β (THRB) gene or the thyroid hormone receptor-α (THRA) gene. RTH caused by THRB mutations (RTH-β) is characterized by the target tissue's response to thyroid hormone, high levels of triiodothyronine and/or thyroxine, and inappropriate secretion of thyroid-stimulating hormone (TSH). THRA mutation is characterized by hypothyroidism that affects gastrointestinal, neurological, skeletal, and myocardial functions. Most patients do not require treatment, and some patients may benefit from medication therapy. These syndromes are characterized by decreased tissue sensitivity to thyroid hormones, generating various clinical manifestations. Thus, clinical changes of resistance to thyroid hormones must be recognized and differentiated, and an approach to the practice of personalized medicine through an interdisciplinary approach is needed.

• Clinical and Experimental Pediatrics
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• v.50 no.6
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• pp.576-579
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• 2007

The syndrome of resistance to thyroid hormone (RTH) is characterized by reduced tissue sensitivity to thyroid hormone (TH). In the majority of subjects, RTH is caused by mutations in the thyroid hormone receptor beta ($TR{\beta}$) gene, located on the chromosome locus 3p24.3. RTH is inherited in an autosomal dominant manner. The clinical presentation of RTH is variable, but common features include elevated serum levels of thyroid hormone (TH), a normal or slightly increased thyrotropin (thyroid stimulating hormone, TSH) level that responds to thyrotropin releasing hormone (TRH), and goiter. We report a 4 year-old girl, who was clinically euthyroid in spite of high total and free $T_4$, and $T_3$ concentrations, while TSH was slightly increased. Sequence analysis of the thyroid hormone receptor beta gene (THRB) confirmed a heterozygous C to T change at nucleotide number 1303, resulting in a substitution of histidine by tyrosine at codon 435 (H435Y). Further analysis of her parents revealed that the H435Y variation was a de novo mutation since neither parents had the variation. Her parents' TH and TSH levels were within normal range.

• Animal cells and systems
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• v.2 no.4
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• pp.489-493
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• 1998

Various heterodimers of the thyroid hormone receptor (TR) with other nuclear hormone receptors confer a wide range of transcriptional activities on thyroid hormone response elements (TREs) in the presence of the thyroid hormone ($T_3$). The present study analyzed the potential roles of retinoid X receptor (RXR) isoforms $\alpha$ and $\beta$ in $T_3$-mediated transcription on a well characterized TRE, a direct repeat of AGGTCA separated by four nucleo-tides (DR4), using electrophoretic mobility shift assays and transient transfection in CV-1 cells. We demonstrated that RXR$\alpha$ supressed liganded $TR_{\alpha}$-induced transcription while $RXR_{\beta}$ did not although both $TR_{\alpha}/RXR_{\alpha}$ and $TR_{\alpha}/RXR_{\beta}$ heterodimers were the predominant forms bound to the TRE-DR4 in the presence of $T_3$. We further demonstrated using Scatchard analysis that the two heterodimers had similar affinities for the TRE-DR4. All these observations suggest that the TRE-DR4 accomodates different types of TR/RXR heterodimers for a more finely tuned transcriptional response to $T_3$.

• Animal cells and systems
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• v.2 no.1
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• pp.133-137
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• 1998

The present study aims to characterize a cDNA encoding zebrafish thyroid hormone receptor $\alpha{1}$ $(zTR\alpha{1)}$ in order to investigate its possible role in the early stage of embryonic development. A mobility shift assay showed that $zTR\alpha{1}$ overexpressed in COS7 cells specifically bound to thyroid hormone response element (TRE). In addition, the specific interaction of anti-rat $TR\alpha{1}$ antibodies with $zTR\alpha1$/TRE complexes demonstrated that the cDNA clone encoded zebrafish thyroid hormone receptor $\alpha{1}$. Transient cotransfection assays showed that $zTR\alpha{1}$ repressed the transcription which was induced by retinoic acid (RA), a well-characterized embryonic morphogen. These results suggest that zTRal may be involved in regulating the RA-induced gene transcription during early embryonic development.

• Biomolecules & Therapeutics
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• v.8 no.4
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• pp.285-292
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• 2000

The effects of the members of the same nuclear receptor superfamily (all-trans retinoic acid (RA), thyroid hormone(T3) or hydrocortisone) on proliferation and differentiation in the SK-N-SH neuroblastoma (NB) cell lines were studied. NB cells were treated with RA, T3, or hydrocortisone at concentration of 10$^{-6}$ M or 10$^{-8}$ M for 3 days or 7 days. RA induced concentration- and time-dependent morphologic differentiation(neurite outgrowth and microtubule-associated protein expression) and growth inhibition in NB cells. Treatment of 10$^{-7}$ M T3 for 7 days increased viability and differentiation of NB cells. Treatment of 10$^{-6}$ M hydrocortisone for 7 days increased viability of NB cells. Although these three effectors are members of the same receptor superfamily, the regulation of brain development may be carried out in a different manner.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.3
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• pp.329-337
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• 1999

Thyroid hormone-induced cellular dysfunctions may be associated with changes in the intracellular $Ca^{2+}$ concentration. The ryanodine receptor, a $Ca^{2+}$ release channel of the SR, is responsible for the rapid release of $Ca^{2+}$ that activates cardiac muscle contraction. In the excitation-contaction coupling cascade, activation of ryanodine receptors is initiated by the activity of sarcolemmal $Ca^{2+}$ channels, the dihydropyridine receptors. In hyperthyroidism left ventricular contractility and relaxation velocity were increased, whereas these parameters were decreased in hypothyroidism. The mechanisms for these changes have been suggested to include alterations in the expression and/or activity levels of various proteins. In the present study, quantitative changes of ryanodine receptors and the dihydropyridine receptors, and the functional consequences of these changes in various thyroid states were investigated. In hyperthyroid hearts, $[^3H]ryanodine$ binding and ryanodine receptor mRNA levels were increased, but protein levels of ryanodine were not changed significantly. However, the above parameters were markedly decreased in hypothyroid hearts. In case of dihydropyridine receptor, there were a significant increase in the mRNA and protein levels, and [3H]nitrendipine binding, whereas no changes were observed in these parameters of hypothyroid hearts. Our findings indicate that hyperthyroidism is associated with increases in ryanodine receptor and dihydropyridine receptor expression levels, which is well correlated with the ryanodine and dihydropyridine binding. Whereas opposite changes occur in ryanodine receptor of the hypothyroid hearts.

• Toxicological Research
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• v.21 no.4
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• pp.333-338
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• 2005

Many of thyroid hormones disrupting chemicals induce effects via interaction with thyroid hormone and retinoic acid receptors and responsive elements intrinsic in target cells. We studied thyroid hormones disrupting effects of food additives and contaminants including BHA, BHT, ethoxyquin, propionic acid, sorbic acid, benzoic acid, CPM, aflatoxin B1, cadmium chloride, genistein, TCDD, PCBs and TDBE in recombinant HeLa cells containing plasmid construct for thyroxin responsive elements. The limit of response of the recombinant cells to T3 and T4 was $1\times10^{-12}\;M$. BHA. genistein, cadmium and TBDE were interacted with thyroid receptors with dose-responsive pattern. In addition, BHA, BHT, ethoxyquin, propionic acid, benzoic acid, sorbic acid, and TBDE showed synergism while cadmium chloride antagonism for T3-induced activity. This study elucidates that recombinant HeLa cell is sensitive and high-throughput system for the detection of chemicals that induce thyroid hormonal disruption via thyroid hormone receptors and responsive elements. Also this study raised suspect of BHA. BHT, ethoxyquin, propionic acid, benzoic acid, sorbic acid, TBDE, genisteine and cadmium chloride as thyroid hormonal system disruptors.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.185.3-186
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• 2003

It is well-known that bisphenol A(BPA), an industrial raw material for polycarbonate and epoxy resins, shows estrogenic activity. Recent research from our laboratory has shown that SPA disrupts interaction between thyroid hormone and its receptor in a non-competitive manner, and alters the thyroid-hormone dependent expression of growth hormone(GH) and prolactin(PRL). (omitted)

• Clinical and Experimental Pediatrics
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• v.48 no.8
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• pp.799-805
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• 2005

Hypothyroidism is a deficiency in thyroid hormone secretion by the thyroid gland and a defect in thyroid hormonal receptor activity. It is categorized by the two major forms in children, the one is congenital hypothyroidism and the other is acquired hypothyroidism. Congenital hypothyroidism is one of the commonest treatable causes of mental retardation and occurs in 1 in 3,000-4,000 infants worldwide. Acquired hypothyroidism is a diseases that have an onset usually after 6 months of age and it may be relate to deceleration in linear growth. The objectives of this article are obtain general and practical concepts of congenital and acquired hypothyroidism during infancy, childhood, and adolescence.

• International journal of thyroidology
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• v.10 no.2
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• pp.71-76
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• 2017

Background and Objectives: The role of thyroid-stimulating hormone (TSH) signaling on osteoblastic differentiation is still undetermined. The aim of this study was to investigate the effects of 5-aza-2'-deoxycytidine (5-azacytidine) on TSH-mediated regulations of osteoblasts. Materials and Methods: MG63, a human osteoblastic cell-line, was treated with 5-azacytidine before inducing osteogenic differentiation using osteogenic medium (OM) containing L-ascorbic acid and ${\beta}$-glyceophosphate. Bovine TSH or monoclonal TSH receptor stimulating antibody (TSAb) was treated. Quantitative real-time PCR analyses or measurement of alkaline phosphatase activities were performed for evaluating osteoblastic differentiation. Results: Studies for osteogenic-related genes or alkaline phosphatase activity demonstrated that treatment of TSH or TSAb alone had no effects on osteoblastic differentiation in MG63 cells. However, treatment of 5-azacytidine, per se, significantly increased osteoblastic differentiation and combination treatment of 5-azacytidine and TSH or TSAb in the condition of OM showed further significant increase of osteoblastic differentiation. Conclusion: Stimulating TSH signaling has little effects on osteoblastic differentiation in vitro. However, in the condition of epigenetic modification using inhibitor of DNA methylation, TSH signaling positively affects osteoblastic differentiation in human osteoblasts.