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Studies on the uterus specific regulation of erythropoietin gene expression and the function of erythropoietin in the uterus

Research Project

Project/Area Number 11460043
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用微生物学・応用生物化学
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

NAGAO Masaya (2001)  KYOTO UNIVERSITY, GRADUATE SCHOOL OF BIOSTUDIES, PROFESSOR, 生命科学研究科, 教授 (10237498)

増田 誠司 (1999-2000)  京都大学, 生命科学研究科, 助教授 (20260614)

Co-Investigator(Kenkyū-buntansha) SASAKI Ryuzo  THE UNTVBRSITY OF SIGA PREFECTURE, LIFE STYLE STUDIES, PROFESSOR, 人間文化学部, 教授 (60077378)
MASUDA Seiji  KYOTO UNIVERSITY, GRADUATE SCHOOL OF BIOSTUDIES ASSOSIATE PROFESSOR, 生命科学研究科, 助教授 (20260614)
永尾 雅哉  京都大学, 生命科学研究科, 助教授 (10237498)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥15,600,000 (Direct Cost: ¥15,600,000)
Fiscal Year 2001: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2000: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 1999: ¥6,800,000 (Direct Cost: ¥6,800,000)
Keywordserythropoietin / estrogen / uterus / hypoxia / oviduct / epididymis / angiogenesis / 雌性生殖器官
Research Abstract

Erythropoietic stimulation has been believed to be the sole physiological function of erythropoietin (Epo). Recently, however, the central nervous system and female reproductive organs have been found to produce Epo. To elucidate how Epo expression is regulated in these tissues, ovariectomized mice were given estrogen (E_2) and/or exposed to hypoxia, and the temporal patterns of Epo mRNA levels were examined. E_2 transiently induced Epo mRNA in the uterus but not in the kidney and cerebrum. Interestingly, the uterine Epo mRNA was hypoxia inducible only in the presence of E_2. Epo mRNA level in the kidney and cerebrum were elevated markedly within 4 h after exposure to hypoxia. Although the elevated level of Epo mRNA in the kidney decreased markedly within 8 h despite continuous hypoxia, the high level in the cerebrum was sustained for 【greater than or equal】 24 h, indicating that down regulation operates in the kidney but not in the brain. Thus Epo expression appears to be regulated in a tissue-specific manner, endorsing the tissue-specific function of Epo.
In the next study, we examined other female reproductive organs in the mouse with respect to Epo mRNA expression and its stimuli (E_2 and hypoxia)-induced changes. Although Epo mRNA expression was seen in the ovary and oviduct, the E_2-induced stimulation of Epo mRNA was found only in the oviduct. The E_2-induced stimulation in the oviduct was transient and rapidly downregulated. Epo mRNA expression in the oviduct was hypoxia inducible, in both the presence and the absence of E2.
We found that Epo is also produced in the male reproductive organs. Cultured epididymis produces Epo. Expression of epididymal Epo mRNA was drastically increased in the course of sexual maturation. Expression of Epo mRNA by the interstitial cells between the ductus epididymidis was found by in situ hybridization technique.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Masuda, S.: "Erythropoietic, Neurotrophic, and Angiogenic functions of Erythropoietin and Regulation of Erythropoietin Production"Int. J. Hematol.. 70. 1-6 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Masuda, S.: "The Oviduct Produces Erythropoietin in an Estrogen-and Oxygen-dependent Manner"Am. J. Physiol. Metab.. 278. E1038-E1044 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kambe, T.: "Retinoic Acid Stimulates Erythropoietin Gene Transcription in Embryonic Carcinoma Cells through the direct repeat of a Steroid/Thyroid Hormone Receptor Response Element Half-site in a Hypoxia-response Enhancer"Blood. 96. 3265-3271 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sasaki, R.: "Erythropoietin : Multiple Physiological Functions and Regulation of Biosynthesis"Biosci. Biotech. Biochem.. 64. 1775-1793 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Chikuma, M.: "Tissue-specific regulation of Erythropoietin Production in Mouse Kidney, Brain and Uterus"Am. J. Physiol. Metab.. 279. E1242-E1248 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sasaki, R.: "Pleiotropic Functions and Tissue-specific Expression of Erythropoietin"News on Physiol. Sci.. 16. 110-113 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yasuda, Y.: "Inhibition of Erythropoietin Signaling Destroys Xenografts of Ovarian and Uterine Cancers in Nude Mice"Br. J. Cancer. 84. 836-843 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Masuda, S.: "Discovery of Tissue-specific Regulation of Erythropoietin Expression and Applied Biochemical Study"Nippon Nogeikagaku Kaishi. 75. 1067-1075 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nagao, M.: "Reproductive Biotechnology"Hokutoshobo, Japan. 6/424 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Masuda, S.: "Erythropoietic, Neurotrophic, and Angiogenic Functions of Erythropoietin and Regulation of Erythropoietin Production"Int. J. Hematol.. 70. 1-6 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Masuda, S.: "The Oviduct Produces Erythropoietin in an Estrogen-and Oxygen-dependent Manner"Am. J. Physiol. Metab.. 278. E1038-E1044 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kambe, T.: "Retinoic Acid Stimulates Erythropoietin Gene Transcription in Embryonic Carcinoma Cells through the direct repeat of a Steroid/Thyroid Hormone Receptor Response Element Half-site in a Hypoxia-response Enhancer"Blood. 96. 3265-3271 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sasaki, R.: "Erythropoietin Multiple Physiological Function and Regulation of Biosynthesis"Biosci. Biotech. Biochem.. 64. 1775-1793 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sasaki, R.: "Pleiotropic functions and Tissue-specific Expression of Erythropoietin"News on Physiol. Sci.. 16. 110-113 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Chikuma, M.: "Tissue-specific Regulation of Erythropoietin Production in Mouse Kidney, Brain and Uterus"Am. J. Physiol. Metab.. 279. 1242-1248 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yasuda, Y.: "Inhibition of Erythropoietin Signaling Destroys Xenografts of Ovarian and Uterine Cancers in Nude Mice"Br. J. Cancer. 84(6). 836-843 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Masuda, S.: "Discovery of Tissue-specific Regulation of Erythropoietin Expression and Applied Biochemical Syudy"Nippon Nogeikagaku Kaishi. 75. 1067-1075 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nagao, M.: "Production of Erythropoetin in Female Reproductive Organs and Its Angiogenic Function in the Uterus Reproductive Biotechnology, (Miyamoto, H. and Manabe, N. Ed)"Hokuoshobo. 147-152 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nagao, M.: "Reproductive Biotechnology"Hokutoshobo, Japan. 6/424 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fujisawa,K.,Yagasaki,K.,Funabiki,R.,Masuda,S.,Sasaki,R.: "Restration of low casein - induced decrease in serum erythropoietin concentration by fortifying diet with methionine and threonine in normal and nephritic rats."Neutrition Research. 20. 685-693 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakamura,Y.,Ohigashi,H.,Masuda,S.,Murakami.A.,Morimitsu,Y.,Kowamoto,Y.Osawa,T.,Imagawa,M.,Uchida,K.: "Redox regulation of glutathione S - transferase induction by benzyl iso thiocyanoric : correlation of enzyme induction with the formation of reactive oxygen intermediates."Cancer Reseorch. 60. 219-225 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sasaki,R.,Masudo,S.,Nagao,M.: "Erythropoietin : Multiple physiological functions and regulation of biosynthesis"Bioscience,Biotechnology and Biochemistry.. 64. 1775-1793 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Chikuina,M.,Masuda,S.,Kobayashi,T.,Nagao,M.,Sasaki,R.: "Tissue - specific regulation of erythropoietin production in the murine kidney, brain and uterus "American Journal fo Physiology. 279. E1242-E1248 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yasuda,Y.,Musha,T.,Tanaka,H.,Fujita,Y.,Fujito,H.,Matsui,T.,Masuda,S.,Nagao,M.,Sasaki,R.,Nakamura,Y.: "Inhibition of erythropoietin signaling destroys Xenogrofts of ovarian and uterine cancers in nude mouse"British Journal of Cancer. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Muramatsu.T.,Arakawa,S.,Fukazawa,K.,Fujiwara,Y.,Yoshida,T.,Sasaki,R.,Masada,S.,Park,H.M: "In vivo gene electroporatism in skeletal muscle with special reference to The duration of gene expression"International Journal of Moleculer Medicine. 7. 37-42 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Masuda S.,Moon S-K.,Kambe T.,Nagao M and Sasaki R.: "A new biological strategy for high productivity of recombinant proteins in animal cells by the use of hypoxia-responsive enhancer"Biotechnology & Bioengineering. 67. 157-164 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Masuda S.,Kobayashi T.,Chikuma M.,Nagao M.and Sasaki R.: "Oviduct produces erythropoietin in an estrogen-and oxygen-dependent manner"American Journal of Physiology. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Masuda S.,Kada E.,Nagao M.and Sasaki R.: "In vitro neuroprotective action of recombinant rat erythropoietin produced by astrocyte cell lines and comparative studies with erythropoietin by chinase hamster ovary cells"Cytotechnology. 29. 207-213 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Masuda S.,Nagao M.and Sasaki R.: "Erythropoietic, neurotrophic, and angiogenic functions of erythropoietin and regulation of erythropoietin production"International Journal of Hematology. 70. 1-6 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 増田誠司,佐々木隆造: "赤血球造血因子 (エリスロポエチン) の生理作用と生合成の調節"健康と栄養のライフサイエンス. 4. 17-22 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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