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Evaluation of in vivo enzymatic activity of cortisol metabolism associated with hypertension

Research Project

Project/Area Number 16590126
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Medical pharmacy
Research InstitutionTokyo University of Pharmacy and Life Sciences

Principal Investigator

KASUYA Yasuji  Tokyo University of Pharmacy and Life Sciences, School of Pharmacy, Professor, 薬学部, 教授 (90096686)

Co-Investigator(Kenkyū-buntansha) FURUTA Takashi  Tokyo University of Pharmacy and Life Sciences, School of Pharmacy, Associate Professor, 薬学部, 助教授 (70120152)
SHIBASAKI Hiromi  Tokyo University of Pharmacy and Life Sciences, School of Pharmacy, Assistant Professor, 薬学部, 講師 (20206121)
YOKOKAWA Akitomo  Tokyo University of Pharmacy and Life Sciences, School of Pharmacy, Assistant, 薬学部, 助手 (70328558)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywordscortisol / cortisone / stable isotope methodology / 11β-activity / urinary cortisone / cortisol ratio / renal disease / hypertension / GC-MS-SIM / グリチルリチン酸 / 体内動態 / 速度論的解析 / 安定同位体標識 / 11β-HSD2酵素活性評価
Research Abstract

This study is associated with a unique approach using stable isotope methodology in evaluating 11β-HSD2 activity in vivo based on urinary excretion of unconjugated (free) cortisol and cortisone. This stable isotope approach offered useful advantages since it allowed to measure stable isotopically labeled cortisol and its labeled metabolite cortisone the potential use of stable isotopically labeled cortisol in man as a tracer for the native cortisol to recognize the conversion of cortisol to cortisone in the kidney. Our results from the stable isotope methodology strongly suggest that the measurement of free cortisol and cortisone in urine is a significant advantage in assessing renal 1lb-HSD2 activity in man.
The kidney is a major site for the conversion of cortisol to cortisone. Since the urinary free cortisone/ cortisol ratio has been proved to be a specific in vivo measure of 11β-HSD2 activity in human kidney reflecting intra-renal concentrations of cortisol and cortisone, a further study was performed to recognize the conversion of cortisol to cortisone catalized by 11β-HSD2 in patients with renal disease.
This study provided direct evidence with regard to the usefulness of a urinary free cortisone/cortisol ratio as an index of human clinical tests for evaluating a reduced 11β-HSD2 activity.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (5 results)

All 2005

All Journal Article (5 results)

  • [Journal Article] Validation of the plasma half-life of 11α-deuterium cortisol as a sensitive index for the analysis of human 11β-HSD2 activity in vivo.2005

    • Author(s)
      Yasuji Kasuya
    • Journal Title

      Steroids 70・12

      Pages: 811-816

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Use of 11 a-deuterium labeled cortisol as a tracer for assessing reduced 11 β-HSD2 activity in vivo following glycyrrhetinic acid ingestion in a human subject.2005

    • Author(s)
      Y.Kasuya, A.Yokokawa, S.Takashima, H.Shibasaki, T.Futruta
    • Journal Title

      Steroids 70-2

      Pages: 117-125

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Validation of the plasma half-life of 1la-deuterium cortisol as a sensitive index for the analysis of human 11β-HSD2 activity in vivo.2005

    • Author(s)
      Y.Kasuya, A.Yokokawa, K.Hamura, H.Shibasaki, T.Futruta
    • Journal Title

      Steroids 70-12

      Pages: 811-816

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Validation of the plasma half-life of 11α-deuterium cortisol as a sensitive indexr for the analysis of 11β-HSD2 activity in vivo.2005

    • Author(s)
      Kasuya Y, Yokokawa A, Hamura K, Shibasaki H, Furuta T
    • Journal Title

      Steroids 70・12

      Pages: 811-816

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Use of 11α-deuterium labeled cortisol as a tracer for assessing reduced 11β-HSD2 activity in vivo following glycyrrhetinic acid ingestion in a human subject2005

    • Author(s)
      Kasuya Y, Yokokawa A, Takashima S, Furuta T, Shibasaki H
    • Journal Title

      Steroids 70・2

      Pages: 117-125

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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