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A comprehensive study on the role of the obese gene product, leptin in reproduction and fetal development

Research Project

Project/Area Number 11470348
Research Category

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

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

SAGAWA Norimasa  Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (00162321)

Co-Investigator(Kenkyū-buntansha) OGAWA Yoshihiro  Kyoto University, Graduate School of Medicine, Instructor, 医学研究科, 助手 (70291424)
KARIYA Masatoshi  Kyoto University, Graduate School of Medicine, Lecturer, 医学研究科, 講師 (90243013)
KONISHI Ikuo  Shinshu University, School of Medicine, Professor, 医学部, 教授 (90192062)
ITOH Hiroaki  Kyoto University, Graduate School of Medicine, Instructor, 医学研究科, 助手 (70263085)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2000: ¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 1999: ¥9,200,000 (Direct Cost: ¥9,200,000)
Keywordsleptin / transgenic mice / reproduction / ovarian function / pregnancy / ingestion / fetal development / placenta / 交感神経系 / 高血圧
Research Abstract

Leptin is an adipocyte-derived hormone that is involved in the regulation of food intake and energy expenditure. Short-term administration of leptin accelerates the onset of puberty in normal mice and corrects the sterility of leptin-deficient ob/ob mice. These findings suggest a putative role of leptin as an endocrine signal between fat depots and the reproductive axis. However, the effect of hyperleptinemia on the initiation and maintenance of reproductive function has not been elucidated. To address this issue, we examined the reproductive phenotypes of female transgenic skinny mice(Tg-mice) with elevated plasma leptin concentrations comparable to those in obese subjects. With no apparent adipose tissue, female Tg-mice exhibit accelerated puberty and intact fertility at younger ages followed by successful delivery of healthy pups. However, at older ages, they develop hypothalamic hypogonadism characterized by prolonged menstrual cycles, atrophic ovary, reduced hypothalamic gonadotro … More pin releasing hormone (GnRH) contents and poor pituitary luteinizing hormone secretion. This study has demonstrated for the first time that accelerated puberty and late onset hypothalamic hypogonadism are associated with chronic hyperleptinemia.
We previously demonstrated that leptin is a novel placenta-derived hormone in humans (Nat Med.3 : 1029, 1997). Intrauterine growth retardation (IUGR) of the fetus due to placental hypoperfusion is one of the most common complications in preeclampsia. In this study, we compared the maternal plasma leptin levels with maternal mean blood pressure and degree of fetal growth restriction. Plasma leptin levels were correlated well with mean blood pressure, but not with body mass index (BMI). Plasma leptin levels in preeclamptic women with IUGR were significantly elevated, compared to those without IUGR (P<0.05). Moreover, plasma leptin levels were negatively correlated with relative birth weight (ΔSD). These dada ggest the possibility that maternal plasma leptin may be useful as a clinical marker of maternal hypertension as well as fetal growth restriction. Less

Report

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

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Norimasa Sagawa, et al.: "Leptin is a Novel Placenta-Derived Hormone in Humans."Taiwanese Journal of Obstetrics and Gynecology. 38. 1-10 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Norimasa Sagawa, et al.: "Leptin as a Novel Placenta-Derived Hormone in Humans.-A Review-"Trophoblast Research. 13. 25-34 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hiroaki Itoh,Norimasa Sagawa, et al.: "Role of Local Guanylate Cyclase System in The Regulation of Ovine Uterine Artery Blood Flow during Pregnancy.-A Review-"Trophoblast Research. 13. 301-309 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Noriomi Matsumura,Norimasa Sagawa, et al.: "Conservative Management of Placenta Accteta without Use of Methotrexate Changes in the Serum Levels of Human Chorionic Gonaobtropin and Pulsatility Index of Uteine Arteies."Journal of Obstetrics and Gynecology Research. 26. 81-87 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shigeo Yura,Yoshihiro Ogawa,Norimasa Sagawa, et al.: "Accelerated Puberty and Late Onset Hypothalamic Hypogonadism in Female Transgenic Skinny Mice Overexpressing Leptin."The Journal of Clinical Investigation. 105. 749-755 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masato Kotani,Issei Tanaka,Norimasa Sagawa, et al.: "Multiple signal transduction pathways through two prostaglandin E receptor EP3 subtype isoforms expressed in human uterus."The Journal of Clinical Endocrinology and Metabolism,. 85. 4315-4322 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoshihiro Ogawa,Hiroaki Masuzaki,Norimasa Sagawa,and Kazuwa Nakao.: "Leptin as an Adpocyte-and Nonadpocyte-Deived Homone In"Pennington Center Nutrition Series,volume 9 Nutrition,Genetics,and Obesity""Louisiana State University Press,Baton Rouge,Louisiana Eds.George A Bray and Donna H Ryan,. 9(147-155) (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoshihiro Ogawa,Norimasa Sagawa, et al.: "Leptin,a novel placenta-derivedhormone in humans.In"Progress in Obesity Research,Volume8""8th International Congress on Obesity.Eds.B.Guy-Grand and G.Aihaud,John Libbey & Company Ltd.,. 5(71-75) (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Norimasa Sagawa, et al.: "Leptin is a Novel Placenta-Derived Hormone in Humans."Taiwanese Journal of Obstetrics and Gynecology. Vol.38. 1-10 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Norimasa Sagawa, et al.: "Leptin as a Novel Placenta-Derived Hormone in Humans.-A Review-"Trophoblast Research. Vol.13. 25-34 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hiroaki Itoh, Norimasa Sagawa, et al.: "Role of Local Guanylate Cyclase System in the Regulation of Ovine Uterine Artery Blood Flow during Pregnancy.-A Review-"Trophoblast Research. Vol.13. 301-309 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Noriomi Matsumura, Norimasa Sagawa, et al.: "Conservative Management of Placenta Accreta without Use of Methotrexate : Changes in the Serum Levels of Human Chorionic Gonadotropin and Pulsatility Index of Uterine Arteries."Journal of Obstetrics and Gynecology Research. Vol.26. 81-87 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shigeo Yura, Yoshihiro Ogawa, Norimasa Sagawa, et al.: "Accelerated Puberty and Late Onset Hypothalamic Hypogonadism in Female Transgenic Skinny Mice Overexpressing Leptin."The Journal of Clinical Investigation. Vol.105. 749-755 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masato Kotani, Issei Tanaka, Norimasa Sagawa, et al.: "Multiple Signal Transduction Pathways through Two Prostaglandin E Receptor EP3 Subtype Isoforms Expressed in Human Uterus."The Journal of Clinical Endocrinology and Metabolism. Vol.85. 4315-4322 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoshihiro Ogawa, Hiroaki Masuzaki, Norimasa Sagawa, and Kazuwa Nakao.: "Leptin as an Adipocyte- and Nonadipocyte-Derived Hormone."In "Pennington Center Nutrition Series, volume 9 Nutrition, Genetics, and Obesity" Eds. George A Bray and Donna H Ryan, Louisiana State University Press, Baton Rouge, Louisiana. 147-155 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoshihiro Ogawa, Norimasa Sagawa, et al.: "Leptin, a Novel Placenta-Derived Hormone in Humans."In "Progress in Obesity Research, Volume 8" Eds. B.Guy-Grand and G.Aihaud, John Libbey & Company Ltd., 8th Intemational Congress on Obesity.. 71-75 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Noriomi Matsumura,Norimasa Sagawa, et al.: "Conservative Management of placenta Aooeta without Use of Methotrexate Changes in the Serum Levels of Human Chorionic Gonadotropin and Pulsatility Index of Uteine Arteries."Journal of Obstetrics and Gynecology Research. 26. 81-87 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shigeo Yura,Yoshihiro Ogawa,Norimasa Sagawa, et al.: "Accelerated Puberty and Late Onset Hypothalamic Hypogonadism in Female Transgenic Skinny Mice Overexpressing Leptin."The Journal of Clinical Investigation. 105. 749-755 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Masato Kotani,Issei Tanaka,Norimasa Sagawa, et al.: "Multiple signal transduction pathways through two prostaglandin E receptor EP3 subtype isoforms expressed in human uterus."The Journal of Clinical Endocrinology and Metabolism. 85. 4315-4322 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takuya Inoue,Noriomi Matsumura,Norimasa Sagawa, et al.: "Severe congenital cytomegalovirus infection with fetal hydrops after maternal recurrent infection."Europian Journal of Obstetrics and Gynecology. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 伊東宏晃,佐川典正 他: "妊娠時子宮動脈血流調節におけるグアニレートサイクレース系の関与."日本妊娠中毒症学会誌. 8. 79-82 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 由良茂夫,佐川典正 他: "ヒト絨毛細胞における肥満遺伝子産物レプチンの産生機序."産婦世界. 52. 239-245 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 佐川典正 他: "レブチンと生殖生理.Annual Review内分泌,代謝2000.編集金澤康徳,他,68-79頁"中外医学社,東京. 12 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 佐川典正: "胎盤におけるレプチンの役割 Biology of Pregnancy―妊娠の生物学 中山徹也 他 編"永井書店、大阪(印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Norimasa Sagawa et al.: "Leptin is a Novel Placenta-Derived Hormone in Humans"Taiwanese Journal of Obstetrics and Gynecology. Vol.38. 1-10 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Norimasa Sagawa et al.: "Leptin as a Novel Placenta-Derived Hormone in Humans.-A Review-"Trophoblast Research. Vol.13. 25-34 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hiroaki Itoh,Norimasa Sagawa et al.: "Role of Local Guanylate Cyclase System in The Regulation of Ovine Uterine Artery Blood Flow during Pregnancy.-A Review-"Trophoblast Research,. Vol.13. 301-309 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kyoko K.Okumura,Norimasa Sagawa,et al.: "Platelet-activating Factor-acetylhydolase Activity and Nitric Oxide Metabolite Level in Plasma of Pregnant Women Who Developed Transient Hypertension Later during Pregnancy"Reproduction, Fertility and Development. Vol.11(in press). (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Noriomi Matsumura,Norimasa Sagawa,et al.: "Conservative Management of Placenta Accreta without Use of Methotrexate: Changes in the Serum Levels of Human Chorionic Gonadotropin and Pulsatility Index of Uterine Arteries"Journal of Obstetrics and Gynecology Research. Vol.26(in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shigeo Yura,Yoshihiro Ogawa,Norimasa Sagawa,et al.: "Accelerated Puberty and Late Onset Hypothalamic Hypogonadism in Female Transgenic Skinny Mice Overexpressing Leptin"The Journal of Clinical Investigation. Vol.105(in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yoshihiro Ogawa, Hiroaki Masuzaki, Norimasa Sagawa, and Kazuwa Nakao.: "Leptin as an Adpocyte-and Nonadpocyte-Derived Hormone In"Pennington Center Nutrition Series, volume 9 Nutrition, Genetics, and Obesity" Eds. George A Bray and Donna H Ryan"Louisiana State University Press, Baton Rouge, Louisiana. 147 - 155 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yoghihiro Ogawa, Norimasa Sagawa, et al.: "Leptin, a novel placenta-derived hormone in humans. In "Progress in Obesity Research, Volume 8" Eds. B. Guy-Grand and G. Aihaud"John Libbey & Company Ltd., 8th International Congress on Obesity. 71 - 75 (1999)

    • Related Report
      1999 Annual Research Report

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

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