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Function of erythropoietin and control of its expression in reproductive organs

Research Project

Project/Area Number 14390045
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 広領域
Research InstitutionThe University of Shiga Prefecture

Principal Investigator

SASAKI Ryuzo  The Univ.Shiga Pre., Dept.of Life style studies, Professor (60077378)

Co-Investigator(Kenkyū-buntansha) 福渡 務  滋賀県立大学, 人間文化学部, 助教授 (50295630)
Project Period (FY) 2002 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥13,300,000 (Direct Cost: ¥13,300,000)
Fiscal Year 2005: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2003: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥3,400,000 (Direct Cost: ¥3,400,000)
Keywordserythropoietin / reproductive organs / testis / epididymis / Quinolinate / Quinolinate metabolism / sperm / 子宮 / 遺伝子除去マウス / フタル酸 / 発達 / 赤血球 / mRNA
Research Abstract

It has been believed that stimulation of erythropoiesis is a sole physiological function of erythropoietin (EPO). But we demonstrated that EPO plays an important role in brain ; EPO exerts neuroprotective function in the central nervous system. Other laboratories have supported this finding. Clinical trial of EPO has been successful for brain damage caused by stroke. In addition we have shown that EPO is also produced in the uterus where EPO acts as an angiogenic factor for periodical growth of uterine endometrial layer. EPO production in the uterus is hypoxia-inducible as it is in the kidney and brain. This project is mainly aimed to explore expression of EPO in the male reproductive organs and to find importance of EPO in these organs.
Testis and epididymis from mice were cultured and EPO in the culture supernatant was assayed. Both organs produced EPO but epididymis produced EPO in much larger amount than testis did. Messenger RNA of EPO was also higher in epididymis than that in testis. Sexual maturation (from 3 weeks to 7 weeks) accompanied remarkable increase of EPO mRNA (120-fold increase) in epididymis. It is possible that EPO is involved in the process by which sperms gain fertility capability, because this event occurs in the epididymis to where sperms are transported from testis.
In the meantime, it was shown that quinolinate (QA), a metabolic intermediate in the metabolic pathway from tryptophan to NAD, inhibits EPO production. When we can accumulate QA and thereby EPO production depressed, we may be able to find a role EPO in the reproductive organs. We have decided to destroy quinolinate phosphoribosyltransferase gene that is responsible for QA metabolism but this project has not yet completed. Phthalate was found to accumulate QA and therefore we may be able to elucidate a role of EPO in the reproductive organs.

Report

(5 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (31 results)

All 2005 2004 2003 2002 Other

All Journal Article (19 results) Book (3 results) Publications (9 results)

  • [Journal Article] Cholesterol is required for the polalized secretion of erythropoietin in Madin-Darby canine kidney cells2005

    • Author(s)
      Maruyama M.
    • Journal Title

      Arch.Biochem.Biophys. 438

      Pages: 174-181

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] エリスロポエチンによる神経細胞保護2005

    • Author(s)
      佐々木 隆造
    • Journal Title

      Clinical Neuroscience 23

      Pages: 909-912

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cholesterol is required for the polarized secretion of erythropoietin in Madin-Darby canine kidney cells.2005

    • Author(s)
      Maruyama M. et al.
    • Journal Title

      Arch.Biochem.Biophys. 438

      Pages: 174-181

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cholesterol is required for the polarized secretion of erythropoietin in Madin-Darby canine kidney cells2005

    • Author(s)
      M.Maruyama
    • Journal Title

      Arch.Biochem.Biophys. 438

      Pages: 174-181

    • Related Report
      2005 Annual Research Report
  • [Journal Article] エリスロポエチンによる神経細胞保護2005

    • Author(s)
      佐々木隆造
    • Journal Title

      Clinical Neuroscience 23

      Pages: 909-912

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Phthalate esters enhance quinolinate production by inhibiting ACMSD, a key enzyme of the tryptophan pathway2004

    • Author(s)
      Fukuwatari T.
    • Journal Title

      Toxicol.Sci. 81

      Pages: 302-308

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Phthalate esters enhance quinolinate production by inhibiting a-amino-β-carboxymuconate-γ-semialdehyde decarboxylase(ACMSD), a key enzyme of the tryptophan pathway.2004

    • Author(s)
      Fukuwatari T. et al.
    • Journal Title

      Toxicol.Sci. 81

      Pages: 302-308

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effects of dietary di(2-ethylhexyl) phthalate on the metabolism of tryptophan to niacin in mice2004

    • Author(s)
      M.Ohta
    • Journal Title

      Exp.Anim. 53

      Pages: 57-60

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Phthalate esters enhance quinolinate production by inhibiting α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase(ACMSD), a key enzyme of the tryptophan pathway2004

    • Author(s)
      T.Fukuwatari
    • Journal Title

      Toxicol.Sci. 81

      Pages: 302-308

    • Related Report
      2004 Annual Research Report
  • [Journal Article] エリスロポエチンの腎外生産とその機能2003

    • Author(s)
      佐々木 隆造
    • Journal Title

      Annual Review 腎臓 2003

      Pages: 116-121

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Pleiofropic functions of erythropoietin2003

    • Author(s)
      Sasaki R.
    • Journal Title

      Internal Medicine 42

      Pages: 142-149

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 脳とエリスロポエチン2003

    • Author(s)
      佐々木 隆造
    • Journal Title

      臨床透析 19

      Pages: 95-97

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Pleiotropic functions of erythropoietin.2003

    • Author(s)
      Sasaki R.
    • Journal Title

      Internal Medicine 42

      Pages: 142-149

    • NAID

      10010530594

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Erythropoietin and erythropoietin-receptor producing cells demonstrated by in situ fybridization in mouse visceral yolk pacs.2002

    • Author(s)
      Yasuda Y.
    • Journal Title

      Anat.Sci.Inter. 77

      Pages: 55-63

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Epididymis is a novel site of erythropoietin production in mouse reproductive organs.2002

    • Author(s)
      Kobayashi T.
    • Journal Title

      Biochem.Biophys.Res.Commun. 296

      Pages: 145-151

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 赤血球を造り脳を獲るエリスロポエチン:作用と組織特異的発現2002

    • Author(s)
      佐々木 隆造
    • Journal Title

      腎とエリスロポエチン研究会(第10回)(中外製薬)

      Pages: 2-4

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Bioengineering of recombinant human erythropoietin.2002

    • Author(s)
      Sasaki R.
    • Journal Title

      Molecular Biology and Clinical Use

      Pages: 308-318

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Erythropoietin and erythropoietin-receptor producing cells demonstrated by in situ hybridization in mouse visceral yolk sacs.2002

    • Author(s)
      Yasuda Y. et al.
    • Journal Title

      Anat.Sci.Inter. 77

      Pages: 58-63

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Epididymis is a novel site of erythropoietin production in mouse reproductive organs.2002

    • Author(s)
      Kobayashi T. et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 296

      Pages: 145-151

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] エリスロポエチンのすべて2005

    • Author(s)
      佐々木 隆造
    • Publisher
      メディカルレビュー社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] エリスロポエチンのすべて(部分執筆)2005

    • Author(s)
      佐々木隆造
    • Publisher
      メディカルレビュー社
    • Related Report
      2005 Annual Research Report
  • [Book] Erythropoietin : Molecular Biology and Clinical Use (W.Jelkmann ed.)2002

    • Author(s)
      Sasaki R.
    • Publisher
      FP Graham Publishing CO.
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Publications] R.Sasaki: "Pleiotropic functions of erythropoietin"Internal Med.. 42. 142-149 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 佐々木隆造: "エリスロポエチンの腎外生産とその機能"Aneual Review肝臓2003. 116-121 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 佐々木隆造: "脳とエリスロポエチン"臨床透析. 19. 95-97 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 佐々木隆造: "脳とエリスロポエチン"臨床透析. 19(印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Y.Yasuda: "Erythropoietin and erythropoietin-receptor producing cells demonstrated by in situ hybridization in mouse visceral yolk sacs"Anat. Sci. Inter.. 77. 58-63 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] T.Kobayashi: "Epididymis is a novel site of erythropoietin production in mouse reproductive organs"Biochem. Biophys. Res. Commun.. 296. 145-151 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Y.Yasuda: "Erythropoietin is involved in growth and angiogenesis in malignant tumors of female reproductive organs"Carcinogenesis. 23. 1797-1805 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 佐々木隆造: "エリスロポエチンの腎外生産とその機能"Annual Review腎臓2003. 116-121 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] R.Sasaki: "Pleiotropic functions of erythropoietin"Internal Med.. 42(印刷中). (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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