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The study of the effects of endocrine disruptors on the hypothalamus-pituitary-gonad axis

Research Project

Project/Area Number 24570074
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Morphology/Structure
Research InstitutionYokohama City University

Principal Investigator

SATO Tomomi  横浜市立大学, 生命ナノシステム科学研究科, 教授 (40295506)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords環境化学物質 / エストロゲン / 卵巣 / 脳下垂体 / 性腺刺激ホルモン / 合成エストロゲン / インヒビン / Notch / notchシグナリング
Outline of Final Research Achievements

To investigate the effects of endocrine disruptors on the hypothalamus-pituitary-gonad axis, LH-secreting gonadotropes and the expression of genes involved in the synthesis and secretion of gonadotropins in the anterior pituitary of neonatally diethylstilbestrol (DES) mice were examined. The percentage of LH-secreting gonadotropes in the medial area of 90-day-old neoDES females was significantly lower than that of 90-day-old neoOil females. Ovariectomy increased the expression of the alpha subunit of glycoprotein hormones, FSH beta subunit and Lhb subunit both in neoOil and neoDES females, suggesting that the anterior pituitary of neoDES female mice is regulated by ovarian hormones via negative feedback. These results suggest that LH-secreting gonadotropes in the female mice are not only directly affected by neoDES but also are influenced by the masculinization of the hypothalamus. That is, neonatal DES exposure can masculinize or defeminize the hypothalamus of female mice.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (20 results)

All 2015 2014 2013 2012 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (13 results)

  • [Journal Article] Effects of diethylstilbestrol (DES) on luteinizing hormone-producing cells in the mouse anterior pituitary.2014

    • Author(s)
      Ishikawa M., Murai E., Hashiguchi Y., T. Iguchi and T. Sato
    • Journal Title

      Exp. Biol. Med.

      Volume: 239 Issue: 3 Pages: 311-319

    • DOI

      10.1177/1535370213519722

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cholesterol homeostasis in the ovaries of neonatallydiethylstilbestrol-treated mice2013

    • Author(s)
      Kakuta H, Matsushita A, Arikawa K, Iguchi T, Sato T
    • Journal Title

      Experimental and Clinical Endocrinology& Diabetes

      Volume: 121 Issue: 02 Pages: 94-101

    • DOI

      10.1055/s-0033-1333780

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Epithelial-stromal interactions in the mouse vagina exposed neonatally to diethylstilbestrol.2013

    • Author(s)
      Katoh T, Hayashi S, Iguchi T, Sato T
    • Journal Title

      In Vivo

      Volume: 27 Pages: 333-337

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hedgehog signaling plays roles in epithelial cell proliferation in the neonatal mouse uterus and vagina2012

    • Author(s)
      中島忠章
    • Journal Title

      Cell and Tissue Research

      Volume: 348 Issue: 1 Pages: 239-247

    • DOI

      10.1007/s00441-012-1350-7

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Wnt family genes and their modulation in the ovary-independent and persistent vaginal epithelial cell proliferation and keratinization induced by neonatal diethylstilbestrol exposure in mice.2012

    • Author(s)
      Nakamura T, Miyagawa S, Katsu Y, Watanabe H, Mizutani T, Sato T, Morohashi KI, Takeuchi T, Iguchi T, Ohta Y
    • Journal Title

      Toxicology

      Volume: 296 Issue: 1-3 Pages: 13-19

    • DOI

      10.1016/j.tox.2012.02.010

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] p21 and Notch signalings in the persistently altered vagina induced by neonatal diethylstilbestrol exposure in mice.2012

    • Author(s)
      Nakamura T, Miyagawa S, Katsu Y, Mizutani T, Sato T, Takeuchi T, Iguchi T, Ohta Y
    • Journal Title

      J Vet Med Sci

      Volume: 74 Pages: 1589-1595

    • NAID

      130001879705

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sequential changes in the expression of Wnt- and Notch-related genes in the vagina and uterus of ovariectomized mice after estrogen exposure.2012

    • Author(s)
      Nakamura T, Miyagawa S, Katsu Y, Sato T, Iguchi T, Ohta Y
    • Journal Title

      In Vivo

      Volume: 26 Pages: 899-906

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Effects of developmental exposure to endocrine disruptors on female organs of mice.2015

    • Author(s)
      Sato T.
    • Organizer
      Special Seminar at Hollings Marine Laboratory, Medical University of South Carolina
    • Place of Presentation
      Charleston
    • Year and Date
      2015-03-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] Regulation of Cyp17a1 expression in the theca cell of mice in vivo and in vitro.2015

    • Author(s)
      Kakuta H. and T. Sato
    • Organizer
      The 97th Annual meeting of the Endocrine Society
    • Place of Presentation
      San Diego
    • Year and Date
      2015-03-05 – 2015-03-08
    • Related Report
      2014 Annual Research Report
  • [Presentation] Induction of Polyovular follicles by diethylstilbestrol and notch signaling pathway in the ovary of neonatal mouse.2015

    • Author(s)
      Terauchi K.J. and T. Sato
    • Organizer
      The 97th Annual meeting of the Endocrine Society
    • Place of Presentation
      San Diego
    • Year and Date
      2015-03-05 – 2015-03-08
    • Related Report
      2014 Annual Research Report
  • [Presentation] Synthesis of retinoic acid and its signaling in the mouse ovary.2015

    • Author(s)
      Shimizu Y. and T. Sato
    • Organizer
      The 97th Annual meeting of the Endocrine Society
    • Place of Presentation
      San Diego
    • Year and Date
      2015-03-05 – 2015-03-08
    • Related Report
      2014 Annual Research Report
  • [Presentation] Reproductive abilities in mice neonatally exposed to 17α-hydroxyprogesterone caproate.2014

    • Author(s)
      Nishizawa H., Kohno S., Guillette Jr L.J., Miyagawa S., Iguchi T. and T. Sato T
    • Organizer
      The 39th Annual meeting of Japan Society for Comparative Endocrinology
    • Place of Presentation
      Okazaki
    • Year and Date
      2014-11-07 – 2014-11-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] Induction of polyovular follicles by diethylstilbestrol and notch signaling pathway in the neonatal mouse ovary.2014

    • Author(s)
      Terauchi K. and T. Sato
    • Organizer
      The 39th Annual meeting of Japan Society for Comparative Endocrinology
    • Place of Presentation
      Okazaki
    • Year and Date
      2014-11-07 – 2014-11-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] 卵巣内におけるレチノイン酸の働きについて2014

    • Author(s)
      清水優貴, 角田華子, 佐藤友美
    • Organizer
      日本動物学会第85回大会
    • Place of Presentation
      仙台
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] ゴナドトロピンによるマウス卵巣ステロイド合成の制御機構について2014

    • Author(s)
      角田華子, 佐藤友美
    • Organizer
      日本動物学会第85回大会
    • Place of Presentation
      仙台
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] Altered estrogenic responsiveness in the adult mouse transcriptome following neonatal exposure to 17α-hydroxyprogesterone caproate.2014

    • Author(s)
      Kohno, S., Sato, T., Miyagawa, S., Newman, R., Iguchi, T. and Guillette L.J. Jr.
    • Organizer
      34th Annual Meeting of the Society for Maternal-Fetal Medicine
    • Place of Presentation
      New Orleans
    • Related Report
      2013 Research-status Report
  • [Presentation] マウス卵巣における濾胞形成時の顆粒膜細胞増殖と基底膜の変化2013

    • Author(s)
      重田祐利,佐藤友美
    • Organizer
      日本動物学会第84回大会
    • Place of Presentation
      岡山大学
    • Related Report
      2013 Research-status Report
  • [Presentation] レチノイン酸シグナルによる子宮間質の運命決定2013

    • Author(s)
      中島忠章, 佐藤友美, 友岡康弘
    • Organizer
      日本動物学会第84回大会
    • Place of Presentation
      岡山大学
    • Related Report
      2013 Research-status Report
  • [Presentation] 胎仔期から成熟期にかけての子宮と膣の分化におけるレチノイン酸シグナルの役割

    • Author(s)
      中島忠章, 井口泰泉, 佐藤友美
    • Organizer
      日本動物学会第83回大会
    • Place of Presentation
      大阪大学豊中キャンパス
    • Related Report
      2012 Research-status Report
  • [Presentation] 新生仔期マウスの子宮と膣におけるエストロゲン受容体α (ERα)の役割

    • Author(s)
      谷本祐樹,佐藤友美
    • Organizer
      日本動物学会第83回大会
    • Place of Presentation
      大阪大学豊中キャンパス
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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