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Pathophysiology and molecular genetics of familial cortisol resistance

Research Project

Project/Area Number 62480254
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionOsaka University(Medical School)

Principal Investigator

MORIWAKI Kaname  Osaka University Medical School Associate Professor, 医学部, 助教授 (90028548)

Co-Investigator(Kenkyū-buntansha) TAJIMA Koji  Osaka University Medical School Research Assistant, 医学部, 助手 (60188240)
IIDA Sayomi  Osaka University Medical School Research Assistant, 医学部, 助手 (40159554)
Project Period (FY) 1988 – 1989
Project Status Completed (Fiscal Year 1988)
Budget Amount *help
¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 1988: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1987: ¥4,300,000 (Direct Cost: ¥4,300,000)
KeywordsGlucocorticoid / Glucocorticoid receptors / Cortisol resistance / Fibroblast, Epstein-Barr virus transforned B-ltymphoytes / 繊維芽細胞 / EーBウィルス / E-Bウィルス / グルココルチコイド抵抗症 / 末稍リンパ球 / 培養線維芽細胞
Research Abstract

In 1985, we found a family (the mother and son) with cortisol resistance. Through investigations of literature revealed that the family was the second family in the world with this disorder. Thus, our study confirmed the presence of such a clinical entity in human beings. Plasma cortisol levels of these patients were surprisingly high in the absence of any of clinical manifestations of cushing's syndrome. The number of glucocorticoid receptors in peripheral blood mononuclear cells of the patients was decreased to 50% of normal subjects.
In order to demonstrate the resistance of the patient's cells to glucucurticoid, in vitro, we cultured the patient's skin fibroblasts and stdied the effect of dexamethasone on the proliferation of the cells. We successfully demonstrated that higher concentrations of dexamethasone were required to suppress thymidine uptake by the patient's cells than normal fibroblasts. The results indicate that the patient's cells are resistant to glucocorticoids.
To further elucidate the nature of glucocorticoid receptors in the patients, we established Epstein-Barr virus transtormed B-lymphocytes clones. In these cells, the number of glucocorticoid receptors was also decreased to one-half of normals. This finding provided evidence that the genetical abnormality was also expressed in these cells and the cells had potential advantages for further genetical analyses.

Report

(3 results)
  • 1988 Annual Research Report   Final Research Report Summary
  • 1987 Annual Research Report
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] 五味正裕: Hormone and Metabolic Researches. 19. 328-330 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 飯田さよみ: Cancer Research. (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 森脇要: "Glucocorticoid receptors:Evolution,structure,function and abnormalities." Waverly Press, ca.100 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Masahiro,Gomi: "In vitro studies of skin fibroblasts from a patient with a new type of primary cortisol resistance." Hormone and Metabolic Researches. 19. 328-330 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Sayomi,Iida: "Properties of glucocorticoid receptors' in Epstein-Barr virus-transfomed B-lymphocytes from patients with familial cortisol resistance." Cancer Research. (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Kaname,Moriwaki: Glucocorticoid Receptors: Evolution, structure, function and abnormalities.Waverly Press, 100 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 五味正裕: Hormone Metabol.Res.19. 328-330 (1987)

    • Related Report
      1988 Annual Research Report
  • [Publications] 飯田さよみ: Cancer Res.(1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] 森脇要: "Glucocorticoid Receptors" Waverly Press, 1-105 (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] Gomi,M,: Hormone f Metabolic Research. 19. 328-330 (1987)

    • Related Report
      1987 Annual Research Report

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Published: 1987-04-01   Modified: 2016-04-21  

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