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Molecular Mechanisms of Expression of TSHR and Graves' Ophthaolmopathy

Research Project

Project/Area Number 10671032
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionYamanashi Medical University

Principal Investigator

HARAGUCHI Kazutaka  Yamanashi Medical University, Assistant Professor, 医学部, 講師 (70165009)

Co-Investigator(Kenkyū-buntansha) IKEDA Masato  Yamanashi Medical University, Medical Staff, 医学部, 医員 (20242638)
SHIMURA Hiroki  Yamanashi Medical University, Assistant, 医学部, 助手 (40303416)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥2,300,000 (Direct Cost: ¥2,300,000)
Keywordsthyrotropin receptor / adipocyte / cytokine / differentiation
Research Abstract

We have shown that functional TSHR has been expressed in rat adipose tissue and 3T3-L1 cells upon differentiation. Since the amount of expressed TSHR approaches to that of thyroid and also enlargement of fat tissue has been reported in Graves' ophthalmopathy, we believe that the exploration of mechanisms of TSHR expression is important for the understanding of pathogenesis of Graves' ophthalmopathy. Using rat preadipocyte and 3T3-L1 cultured cells, we obtained the findings below.
1 ) Dedifferentiation of adipocyte by cytokines such as TGFィイD2βィエD2, TNFィイD2αィエD2 and IFNィイD2γィエD2 was accomopanied by the decreased expression of TSHR.
2)Stimulation of differentiation of adipocytes by PPARィイD2γィエD2 activators was accompanied by the increased expression of TSHR whose responsiveness to TSH was well conserved.
3)Transfection of preadipocytes with PPARg expressing adenovirus enhanced the PPARg activators on its actionon TSHR expression.
4)Deoxyribonuclease 21 protection showed that nuclear extracts from differentiated 3T3-L1 cells strongly protected two sequences from -146 to -127 and -112 to -106 containing Ets-binding sites.
5)We found two new nuclear proteins which binds to putative Ets binding site of TSHR, one decreased upon differentiation whereas the other increased.
Using southwestern analysis, we are now trying to identify and get clonnes of the new nuclear proteins.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (9 results)

All Other

All Publications (9 results)

  • [Publications] K.Haraguchi他: "Effects of throtropin on the proliferation and differention of cultured rat preadipocytes"Thyroid. 9. 613-619 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K.Haraguchi他: "Effects of Cytokines on Expression of Thyrotropin Receptor mRNA in Rat Preadipocytes"Thyroid. 8. 687-692 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H.Shimura他: "Analysis of Differentiation-induced Expression Mechanism of Thyrotropin recep Gene in Adipocytes"Molecular Endocrinology. 12. 1473-1486 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. Haraguchi et al.: "Effects of thyrotropin on the proliferation and differentitation of cultured rat preadipocytes."Thyroid. 9. 613-619 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. Haraguchi et al.: "Effects of Cytokines on Expression of Thyrotropin Receptor mRNA in Rat Preadipocytes."Thyroid. 8. 687-692 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H. Shimura et al.: "Analysis of Differentitation-induced Expression Mechanism of Thyrotropin recep Gene in Adipocytes."Molecular Endocrinology. 12. 1473-1486 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K.Haraguchi 他: "Effects of thyrotropin on the proliferation and differentitation of cultured rat preadipocytes."Thyroid. 8. 613-619 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] H.Shimura 他: "Analysis of Differentiation-induced Expression Mechanism of Thyrotropin Receptor Gene in Adipocytes" Molecular Endocrinology. 12. 1473-1486 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Haraguchi 他: "Effect of Cytokines on Expression of Thyrotropin Receptor mRNA in Rat Preadipocytes" THYROID. 8. 687-692 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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