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Analysis of Neurosteroids and Its Application to Development of Anti-dementia Medicine

Research Project

Project/Area Number 09557188
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Physical pharmacy
Research InstitutionKanazawa University

Principal Investigator

SHIMADA Kazutake  Kanazawa University, Graduate School of Natural Science and Technology ; Professor, 自然科学研究科, 教授 (90004605)

Co-Investigator(Kenkyū-buntansha) HONMA Seijiro  Teikoku Hormone Mfg Co. ; Head Research Director, 代謝部, 主席研究員
HIGASHI Tatsuya  Kanazawa University, Faculty of Pharmaceutical Science ; Assistant, 薬学部, 助手 (90272963)
MITAMURA Kuniko  Kanazawa University, Faculty of Pharmaceutical Sciences ; Assistant, 薬学部, 助手 (70242526)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥13,200,000 (Direct Cost: ¥13,200,000)
Fiscal Year 1998: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 1997: ¥9,100,000 (Direct Cost: ¥9,100,000)
KeywordsBrain / Neurosteroid / Oxosteroid / Classical estrogen / Guaiacol estrogen / Stress / LC / MS / GC / 増加 / エストロゲン
Research Abstract

The term neurosteroids applies to those steroids that are both synthesized in the nervous system, either de novo from cholesterol or from steroid hormone precursors, and that accumulate in the nervous system to levels that are at least in part independent of steroidogenic gland secretion rates. Neurosteroids consist of 17- or 20-oxosteroids and accumulate in brains as unconjugated form and their sulfates, fatty acid esters and sulfolipid conjugates.
An assay method for pregnenolone and its 3-stearate in brains has been developed using liquid chromatography/atmospheric pressure chemical ionization mass spectrometry (LC/APCI-MS) operating in the positive ion mode. The method was applied to the determination of these steroids in the gray matters and olfactory bulbs of rat brains. Although pregnenolone in both regions of the rat brains increased more than five times after acute stress, its 3-stearate decreased after the stress.
The existence of classical and guaiacol estrogens in rat brains were also clarified using GC/MS^n. The usefulness of estrogen replacement therapy for dementia of the Alzheimer type and the existence of the estrogen receptor in brains have been reported, our data suggested that estrogen exists in brains as neurosteroids or neuroactive steroids.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] K.Shimada: "Studies on neurosteroids V.Separation and characterization of pregnenolone 3-stearate in rat brains using high-performance liquid chromatography" J.Chromatogr.Sci.35. 71-74 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Shimada: "Studies on neurosteroids VI.Characterization of fatty acid esters of pregnenolone and dehydroepiandrosterone in rat brains using liquid chromatography-mass spectrometry" Anal.Commun.34. 145-146 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 島田和武: "脳内ステロイドホルモンの分析" 薬誌. 117. 681-689 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Shimada: "Studies on neurosteroids VII.Characterization of pregnenolone,its sulfate,and dehydroepiandrosterone in rat brains using liquid chromatography/mass spectrometry" J.Liq.Chromatogr.Relat.Technol.21. 765-775 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Shimada: "Studies on neurosteroids VIII.Determination of pregnenolone and its 3-stearate in rat brains using.high-pertormance liquid chromatography-atmospheric pressure chemical ionization mass spectrometry" J.Chromatogr.B. 714. 153-160 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Shimada: "Studies on neurosteroids IX.Characterization of estrogens in rat brains using gas chromatography/tandem mass spectrometry" J.Chromatogr.A. in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Shimada et al.: "Studies on neurosteroids V.Separation and characterization of pregnenolone 3-stearate in rat brains using high-performance liquid chromatography." J.Chromatogr.Sci.35(2). 71-74 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Shimada et al.: "Studies on neurosteroids VI.Characterization of fatty acid esters of pregnenolone and dehydroepiandrosterone in rat brains using liquid chromatography-mass spectrometry." Anal.Commun.34(5). 145-146 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Shimada: "Analysis of neurosteroids" Yakugaku Zasshi. 117(10-11). 681-689 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Shimada et al.: "Studies on neurosteroids VII.Characterization of pregnenolone, its sulfate, and dehydroepiandrosterone in rat brains using liquid chromatography/mass spectrometry." J.Liq.Chromatogr.Relat.Technol.21(6). 765-775 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Mitamura, K.Shimada: "Derivatization in LC/MS" Yakugaku Zasshi. 118(6). 206-215 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Shimad a et al.: "Studies on neurosteroids VIII.Determination of pregnenolone and its 3-stearate in rat brains using high-performance liquid chromatography-atmospheric pressure chemical ionization mass spectrometry." J.Chromatogr.B. 714(2). 153-160 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Shimada et al.: "Studies on neurosteroids IX.Characterization of estrogens in rat brains using gas chromatography/tandem mass spectrometry." J.Chromatogr.A. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Shimada: "Studies on neurosteroids VII. Characterization of pregnenolone,its sulfate,and dehydroepiandrosterone in rat brains using liquid chromatography/mass spectrometry" J.Liq.Chromatogr.Relat.Technol.21・6. 765-775 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 三田村邦子: "LC/MSにおける誘導体化" 薬誌. 118・6. 206-215 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Shimada: "Studies on neurosteroids VIII.Determination of pregnenolone and its 3-stearate in rat brains using high-performance liquid chromatography-atmospheric pressure chemical ionization mass spectrometry" J.Chromatogr.B. 714・2. 153-160 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Shimada: "Studies on neurosteroids IX.Characterization of estrogens in rat brains using gas chromatography/tandem mass spectrometry" J.Chormatogr.A. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Kazutake SHIMADA: "Studies on neurosteroids V. Separation and characterization of pregnenolone 3-stearate in rat brains using high-performance liquid chromatography." J.Chromatogr.Sci.,. 35・2. 71-74 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kazutake SHIMADA: "Studies on neurosteroids VI.Characterization of fatty acid esters of pregnenolone and dehydroepiandrosterone in rat brains using liquid chromatography-mass spectrometry." Anal.Commun.,. 34・5. 145-146 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 島田和武: "脳内ステロイドホルモンの分析" 薬誌、,. 117・10〜11. 681-689 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kazutake SHIMADA: "Studies on neurosteroids VII.Characterization of pregnenolone,its sulfate,and dehydroepiandrosterone in rat brains using liquid chromatograph/mass spectrometry." J.Liq.Chromatogr.Relat.Techno.,. (in press).

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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