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Study on the Pathogenesis of Graves' Ophthalmopathy using 3T3-L1 Cells Which Express Thyrotropin Receptor

Research Project

Project/Area Number 08671143
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内分泌・代謝学
Research InstitutionYamanashi Medical University

Principal Investigator

HARAGUCHI Kazutaka  Yamanashi Medical University, The Third Department of Internal Medicine, Lecturer, 医学部, 講師 (70165009)

Co-Investigator(Kenkyū-buntansha) SHIMURA Hiroki  Yamanashi Medical University, The Third Department of Internal Medicine, Medical, 医学部, 医員
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1997: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1996: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsTSH / 3T3-L1 / differentiation / PPAR_<gamma> / 前脂肪細胞 / 3T3-L1
Research Abstract

It has been speculated that thyrotripin Receptor (TSHR) elicites the autoimmune reaction in retroorbital tissues in Graves' patlents and causes the ophthalmopathy. We investigated the molecular mechanisms of expression in rat adipocytes and 3T3-L1 cells.
Results : TSHR is expressed in the presence of insulin, dexamethazone, and IBMX.Primer extension and cloned cDNA sequences showed that transcription of TSHR gene in rat adipose tissue was from multiple stasites between -89 to -68. TSH-dependent down regulation of TSHR was observed 1 hr after TSH addition a dis not need protein synthesis. Down regulation was cAMP-dependent. DNase Iprotection assay showed 1 nuclear extracts from differentiated 3T3-L1 cells protected sesquence-146 to -127 which contained cAMP-responsive element. Furthermore, we found another protection site downstream of-127. Gel shift analysis with antibodies against many known transcription factors revealed that the transcription factor (s) which bound to the downstream elements is (were) secific to the adipocytes. We are now identifying the molecule which binds to the downstream element. Finally, we evaluated the effects of various PPAR_<gamma> activators and recombinant adenovirus which expresses PPAR_<gamma>2, and we found that PPAR_<gamma> activators and recombinant adenovirus stimulated the differentiation and the expression of TSHR in 3T3-L1 cells. Express of TSHR was accompanied by the TSH-stimulated cAMP prodction.
Summary : Differentiation of adipocytes are closely related to the expression of TSHR mRNA.There is a complicated mechanism which allow the a enormous amount of expression of TSHR in adipocytes.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Haraguchi K.et al.: "Differentiation of rat preadipocytes is accompanied by expression of thyrotropin receptors." Endocrinology. 137. 3200-3205 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Haraguchi K.et al.: "Functional expression of thyrotropin receptor in differentiated 3T3-L1 cells." Biochem Biophys Res Commun. 223. 193-198 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shimura H.et al.: "Regulation of thyrotropin receptor gene expression in 3T3-L1 adipose cells is distinct from its regulation in FRTL-5 thyroid cells." Endocrinology. 138. 1483-1490 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Haraguchi K.et al.: "Differentiation of rat preadipocytes is accompanied by expression of thyrotropin receptors" Endocrinology. 137. 3200-3205 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Haraguchi K.et al.: "Functional expression of thyrotropin receptor in differentiated 3T3-L1 cells" Biochem Biophys Res Commun. 223. 193-198 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shimura H.et al.: "Regulation of thyrotropin receptor gene expression in 3T3-L1 adipose cells is distinct from its regulation in FRTL-5 thyroid cells." Endocrinology. 138. 1483-1490 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 原口和貴: "Differentiation of rat preadipocytes is accompanied by expression of thyrotropin receptors." Endocrinology. 137. 3200-3205 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 原口和貴: "Functional expression of thyrotropin receptor in differentiated 3T3-L1 cells." Biochem Biophys Res Commun. 223. 193-198 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 志村浩己: "Regulation of thyrotropin receptor gene expression in 3T3-L1 adipose cells is distinct from its regulation in FRTL-5 thyroid cells." Endocrinology. 138. 1483-1490 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Haraguchi,et al.: "Differentiation of Rat Preadipocytes Is Accompanied by Expression of Thyrotropin Receptors" Endocrinology. 137. 3200-3205 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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