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Biomedical subjects

Yuji Hataya

Publications and source records attributed to Yuji Hataya.

7 recordsLinked to original sources
PubMed2006

Antithyroid drugs inhibit thyroid hormone receptor-mediated transcription.

CONTEXT: Methimazole (MMI) and propylthiouracil (PTU) are widely used as antithyroid drugs (ATDs) for the treatment of Graves' disease. Both MMI and PTU reduce thyroid hormone levels by several mechanisms, including inhibition of thyroid hormone synthesis and secretion. In addition, PTU decreases 5'-deiodination of T(4) in peripheral tissues. ATDs may also interfere with T(3) binding to nuclear thyroid hormone receptors (TRs). However, the effect of ATDs on the transcriptional activities of T(3) mediated by TRs has not been studied. OBJECTIVE: The present study was undertaken to determine whether ATDs have an effect on the gene transcription regulated by T(3) and TRs in vitro. METHODS: Transient gene expression experiments and GH secretion assays were performed. To elucidate possible mechanisms of the antagonistic action of ATDs, the interaction between TR and nuclear cofactors was examined. RESULTS: In the transient gene expression experiments, both MMI and PTU significantly suppressed transcriptional activities mediated by the TR and T(3) in a dose-dependent manner. In mammalian two-hybrid assays, both drugs recruited one of the nuclear corepressors, nuclear receptor corepressor, to the TR in the absence of T(3). In addition, PTU dissociated nuclear coactivators, such as steroid receptor coactivator-1 and glucocorticoid receptor interacting protein-1, from the TR in the presence of T(3). Finally, MMI decreased the GH release that was stimulated by T(3). CONCLUSIONS: ATDs inhibit T(3) action by recruitment of transcriptional corepressors and/or dissociation of coactivators. This is the first report to show that ATDs can modulate T(3) action at the transcriptional level.

Antithyroid Agents↗
PubMed2005

A case of type 2 diabetes mellitus developing hypothyroidism discovered as a result of a discrepancy between glycated hemoglobin and glycated albumin values.

We report a case of type 2 diabetes mellitus presenting hypothyroidism due to overeating of seaweed that was noticed as a result of a discrepancy between glycated albumin (GA) and glycated hemoglobin (GHb). A 71-year-old woman was undergoing managed treatment with oral medicines and insulin for diabetes mellitus with no sign of thyroid disease. Her thyroid function was euthyroid without aid of thyroid hormone. All of the patient's thyroid autoantibodies were negative. Fifteen weeks prior to indications of hypothyroidism, she had started to consume large amounts (100-200 g dry weight equivalent) of cooked "wakame" seaweed every morning. Just before admission to our hospital, her GA was 26.9%, while GHb and fasting plasma glucose remained within normal ranges (less than 5.6%, and 106 mg, respectively). This discrepancy between GA and GHb drew our attention to the development of complications. Naive interview of the patient led us to believe a thyroid hormone deficiency existed, though without any related complaints or findings, such as non-pitting edema, cold intolerance, or easy fatiguing. Seaweed consumption was stopped and periodic observation of thyroid function started. As thyroid hormone levels moved into normal range, GA and GHb returned to their normal relative ratio after 3 months. Thus, measurement of the relative ratio of GA and GHb may be useful for glycemic monitoring, with the potential as a readily available glycemic control marker for patients with changeable complications.

Aged↗
PubMed2004

Genomic structure and characterization of the 5'-flanking region of the human ghrelin gene.

Ghrelin, an endogenous ligand for the GH secretagogue receptor, induces GH secretion, food intake, and positive energy balance. Although ghrelin exhibits a variety of hormonal actions, the mechanisms regulating ghrelin expression and secretion remain unclear. To understand regulation of human ghrelin gene expression, we examined the genomic structure of approximately 5,000 bp of the 5'-flanking region of the human ghrelin gene. We performed rapid amplification of cDNA ends to estimate transcriptional start sites, indicating that there are two transcriptional initiation sites within the human ghrelin gene. Both transcripts were equally expressed in the human stomach, whereas the longer transcript was mainly expressed in a human medullary thyroid carcinoma (TT) cell line. Functional analysis using promoter-reporter constructs containing the 5'-flanking region of the gene indicated that the sequence residing within the -349 to -193 region is necessary for human ghrelin promoter function in TT cells. Within this region existed several consensus sequences for a number of transactivating regulatory proteins, including an E-box site. Destruction of this site decreased to 40% of the promoter activity. The upstream region of the promoter has two additional putative E-box sites, and site-directed mutagenesis suggested that these are also involved in promoter activation. Electrophoretic mobility shift assays demonstrated that the upstream stimulatory factor specifically bound to these E-box elements. These results suggest a potential role for upstream stimulatory factor transcription factors in the regulation of human ghrelin expression.

5' Flanking Region↗
PubMed2004

Transgenic mice producing major histocompatibility complex class II molecules on thyroid cells do not develop apparent autoimmune thyroid diseases.

The expression of major histocompatibility complex (MHC) class II molecules on thyrocytes has been demonstrated in autoimmune thyroid diseases. However, the role of this aberrant MHC class II in disease development is controversial. In particular, it remains unknown whether MHC class II expression on thyrocytes, which are nonprofessional antigenpresenting cells, plays a role in inducing autoimmune processes. To clarify this issue, we have produced transgenic mice harboring an MHC class II gene ligated to the promoter of the rat TSH receptor. We obtained three lines of transgenic mice, and the expression of MHC class II by the thyrocytes was demonstrated by immunofluorescence staining and flow cytometry. Our examination revealed no obvious abnormalities in thyroid histology or in thyroid autoantibody production in these transgenic mice. Although serum-free T(4) levels were slightly lower than those of their nontransgenic littermates, no transgenic mouse suffered from clinical hypothyroidism or hyperthyroidism. Furthermore, thyroid lymphocytic infiltration was absent, and MHC class II-expressing thyrocytes obtained from transgenic mice failed to stimulate the proliferation of autologous T cells in vitro. Taken together, these results show that transgenic mice with MHC class II molecules on their thyrocytes do not develop apparent autoimmune thyroid diseases, suggesting that aberrant MHC class II expression alone is not sufficient to induce thyroid autoimmunity.

Animals↗
PubMed2003

Alterations of plasma ghrelin levels in rats with lipopolysaccharide-induced wasting syndrome and effects of ghrelin treatment on the syndrome.

Ghrelin not only strongly stimulates GH secretion, but is also involved in energy homeostasis by stimulating food intake and promoting adiposity through a GH-independent mechanism. These effects of ghrelin may play an important role in the pathophysiology of inflammatory wasting syndrome, in which both the somatotropic axis and energy balance are altered. In this study we investigated plasma ghrelin concentrations after lipopolysaccharide (LPS) administration to rats, a model of the wasting syndrome and critical illness. In addition, the therapeutic potential of the antiwasting effects of ghrelin was explored using LPS-injected rats. A single LPS injection suppressed plasma ghrelin levels 6 and 12 h later. Maximal reduction was observed 12 h after LPS injection, in a dose-dependent manner. In contrast, plasma ghrelin levels were elevated after repeated LPS injections on d 2 and 5. Peripheral administration of ghrelin twice daily (10 nmol/rat) for 5 d increased body weight gain in repeated LPS-injected rats. Furthermore, both adipose tissue weight and plasma leptin concentrations were increased after ghrelin administration in these rats. In conclusion, plasma ghrelin levels are altered in LPS-injected rats, and ghrelin treatment may provide a new therapeutic approach to the wasting syndrome and critical illness.

Adipose Tissue↗
PubMed2002

Thyroid hormone action is disrupted by bisphenol A as an antagonist.

Bisphenol A (BPA), a monomer of polycarbonate plastics, has been shown to possess estrogenic properties and act as an agonist for the estrogen receptors. Although an epidemiologically based investigation has suggested that some chemicals could disrupt thyroid function in animals, the effects on thyroid hormone receptors (TRs) are unknown. We show here that BPA inhibits TR-mediated transcription by acting as an antagonist. In the transient gene expression experiments, BPA suppressed transcriptional activity that is stimulated by thyroid hormone (T(3)) in a dose-dependent manner. The inhibitory effects were observed in the presence of physiological concentrations of T(3). In contrast, in the case of negatively regulated TSHalpha promoter, BPA activated the gene transcription that is suppressed by T(3). To elucidate possible mechanisms of the antagonistic action of BPA, the effects on T(3) binding and cofactor interaction with TR were examined. The K(i) value for BPA was 200 micro M when assessed by inhibition of [(125)I]T(3) binding to rat hepatic nuclear TRs. In a mammalian two-hybrid assay, BPA recruited the nuclear corepressor to the TR. These results suggest that BPA could displace T(3) from the TR and recruit a transcriptional repressor, resulting in gene suppression. This is the first report that BPA can antagonize T(3) action at the transcriptional level. BPA may disrupt the function of various types of nuclear hormone receptors and their cofactors to disturb our internal hormonal environment.

Animals↗