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Development of inhibitor for 20a-hydroxysteroid dehydrogenase

Research Project

Project/Area Number 05556052
Research Category

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

Allocation TypeSingle-year Grants
Research Field Basic veterinary science/Basic zootechnical science
Research InstitutionThe University of Tokyo

Principal Investigator

SHIOTA Kunio  Faculty of Agriculture, The University of Tokyo, Associate Professor, 農学部, 助教授 (80196352)

Co-Investigator(Kenkyū-buntansha) NODA Ken  Faculty of Agriculture, The University of Tokyo, Assistant Professor, 農学部, 助手 (60218287)
ASANO Toshihiko  National Institute of Health, Department of Veterinary Science, Section Chief, 室長 (60100062)
SASAKI Nobuo  Faculty of Agriculture, The University of Tokyo, Professor, 農学部, 教授 (60107414)
TAKAHASI Michio  Faculty of Agriculture, The University of Tokyo, Professor, 農学部, 教授 (30011943)
OGAWA Tomoya  Faculty of Agriculture, The University of Tokyo, Professor, 農学部, 教授 (30087572)
Project Period (FY) 1993 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥16,000,000 (Direct Cost: ¥16,000,000)
Fiscal Year 1995: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1994: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 1993: ¥8,800,000 (Direct Cost: ¥8,800,000)
Keywords20alpha-hydroxysteroid dehydrogenase / Progesterone / 20alpha-dihydroprogesterone / Enzyme inhibitor / Steroid derivatives / neoplasm / Ovary / Immunecells / 活性阻害試薬 / 株化腫瘍細胞 / 黄体細胞 / 乳腺癌細胞 / 骨肉腫 / ヌードマウス
Research Abstract

20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) is an enzyme which catalizes progesterone to a biologically inactive steroid 20alpha-dihydroprogesterone (4-pregnen-20a-ol-3-one : 20alpha-OHP). The activity of this enzyme is found to be distributed in endocrine tissues including the ovary, testis, placenta and adrenal gland. Since progesterone is the precursor of biologically active steroids such as an androgen, estrogen, and corticoid, an increase in this enzyme may alter the regulation of their secretion. 20alpha-HSD is also distributed in a variety of tisuues including T-cells, Macrophage and erthrocytes. Interestingly, enzyme activity is found in spontaneous neoplasms of animals. 20alpha-HSD activity was found in the tissue surrounding the fetus during pregnancy in the rat except for the specific period during which spontaneous fetus loss occurs. Although physiological or pathological role role of 20alpha-HSD has not been determined, it is clear that the enzyme plays a role other than the regulation of steroid secretion and 20alpha-HSD mat be important in may biological process including cytodifferentiation and survival of the cells. To clarify these problems, development of specific inhibitors for 20alpha-HSD has been needed and various steroid derivatives have screened. In the series of the experiment, the derivatives @92STZ-26 is selsected as 20alpha-HSD.This derivative is effective to inhibit purified 20alpha-HSD activity under the invitro condition and in vivo condition.

Report

(4 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] K.Yamanouchi,他: "Effect of calyculin-A, phosphatase inhibitor on 20α-hydroxysteoid dehyclrogenase activity in rat luteal cell culture." Endocrine J.,. 40. 699-704 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Noda, 他: "Rat Ovarian 20α-hydroxysteroid clehyrogenasa-1 may belong to aldo-keto redyctase supertamily." J. Reprod. Dev.39. 169-173 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Shiota, 他: "20α-hydroxysleroid dehydrogenase activity in rat placenta." Endocrine J.,. 673-681 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] R. Miura, 他: "Molecular cloning of cDNA for rat ovarian 20α-hydroxysteroid dehydrogenase(HSDI)" Biochem. J,. 299. 561-567 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] N. M. Tanaka, 他: "20α-hydroxysteoid dehydrogenase activity in canine spontaneous neoplasm." J.Vet. Med. Sci,. 56. 581-583 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] N. M. Tanaka, 他: "Effect of 20α-hydroxysteroid dehydrogenase and its inhibitors on canine osteosarcoma cell growth in vitro." J.Vet. Med. Sci,. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Yamanouchi et.al: "Effect of calyculin-A,phosphatase inhibitor on 20alpha-hydroxysteroid dehydrogenase activity in rat luteal cell culture" Endocrine J. 40. 699-704 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Noda et.al: "Rat Ovarian 20alpha-hydroxysteroid dehydrogenase-1 may belong to aldo-keto reductase superfamily." J.Reprod.Dev. 39. 169-173 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Shiota et.al: "20alpha-Hydroxysteroid dehydrogenase activity in rat placenta." Endocrine J. 673-681 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] R.Miura et.al: "Molecular cloning of cDNA for rat ovarian 20alpha-hydroxysteroid dehydrogenase (HSD1)." Biochem.J. 299. 561-567 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] N.M.Tanaka et.al: "20alpha-hydroxysteroid dehydrogenase activity in canine spontaneous neoplasm." J.Vet.Med.Sci. 56. 581-583 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] N.M.Tanaka et.al: "Effect of 20alpha-hydroxysteroid dehydrogenase and its inhibitors on canine osteosarcoma cell growth in vitro." J.Vet.Med.Sci. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shiota, K. 他: "Structural and functional aspects of placental lactogens(PLs) and ovavian 20α-Hydroxysterold dehydrogenase (20α-HSD)in the rat" Endocrine J.41(Supl). 43-56 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ishimura R. 他: "Glycoliped composition of rat placenta: changes in glycosphingolipids associated with pregnancystage." Mol. Cell. Endocr.115. 149-159 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Shiota K. 他: "Molecular diversity of rat placental lactogens." Trophoblast Research. 19. (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] K.Shiota他: "Structural and functional aspects of placeutal lactogens(PLs)and ovarian 20α-hydroxysteroid dehydrogenase(20α-HSD)in the rat." Endocrine J.,. 41(Supl). S43-S56 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] R.Miura他: "Molecular cloning of CDNA for rat ovarian 20α-hydroxysteroid dehydrogenase(HSDL)." Biochem.J.,. 299. 561-567 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] N.M.Tanaka他: "20α-hydroxysteroid dehydrogenase activity in canine spontaneous neoplasm." J.Vet.Med.Sci.,. 56. 581-583 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] K.Noda: "Rat ovarian 20α-hydroxysteroid dehydrogenase-1 may belong to aldo-keto reductase superfamily." J.Reprod.Develop.39. 169-173 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] R.Miura: "Molecular cloning of rat ovarian 20α-hydroxysteroid dehydrogenase." Biol.Reprod.48. 134 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] K.Shiota: "20α-hydroxysteroid dehydrogenase activity in rat placenta." Endocrine J.40. 673-681 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] K.Noda: "Charocterization of anti rat ovarian 20α-hydroxysteroid dehydrogenase IgG." J.Reprod.Develop.(in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] R.Miura: "Molecular cloning of cDNA for rat ovarian 20α-hydroxysteroid dehydrogenase,type1." Biochem.J.(in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] M.Tanaka: "20α-hydroxysteroid dehydrogenase activity in canine spontaneous neoplasms." J.Vet.Med.Sci.(in press). (1994)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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