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Androgen-induced signaling and sexual differentiation of reproductive organs

Research Project

Project/Area Number 25281026
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Risk sciences of radiation and chemicals
Research InstitutionGifu Pharmaceutical University

Principal Investigator

NAKANISHI TSUYOSHI  岐阜薬科大学, 薬学部, 准教授 (50303988)

Co-Investigator(Kenkyū-buntansha) 永瀬 久光  岐阜薬科大学, 薬学部, 教授 (40141395)
Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2016: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Keywordsアンドロゲン / 性分化 / 17β-ヒドロキシステロイド脱水素酵素 / 胎生期・発達期影響 / トランスジェニックマウス
Outline of Final Research Achievements

Androgens play a major role in male sexual development. Although androgen-induced masculinization has been well studied, genuine role of androgens in reproductive development remains unclear. To study the direct effect of androgens in reproductive development, we generated a transgenic mouse that carries a transgene expressing EGFP-tagged 17β-hydroxysteroid dehydrogenase type 3 (17β3E), which converts androstenedione into testosterone, based on the Cre/loxP recombination (17β3ETG mouse). When 17β3ETG mice were mated with Cre-expressing TG mice, testosterone and dihydrotestosterone levels in the 17β3E/Cre double TG fetuses (DTG) were significantly higher than those of the 17β3E single TG littermates in both male and female. Consistent with these results, female DTG has formed male reproductive tracts in the prenatal and postnatal period. These results suggest that our model mice are potential tool for investigating genuine role of androgens in reproductive development.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (51 results)

All 2017 2016 2015 2014 2013 Other

All Int'l Joint Research (2 results) Journal Article (11 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 11 results,  Open Access: 5 results,  Acknowledgement Compliant: 2 results) Presentation (38 results) (of which Int'l Joint Research: 3 results,  Invited: 8 results)

  • [Int'l Joint Research] Peking University(China)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] Peking University(China)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Fluorene-9-bisphenol is anti-oestrogenic and may cause adverse pregnancy outcomes in mice2017

    • Author(s)
      Zhaobin Zhang 他15名
    • Journal Title

      Nature Communications

      Volume: 8 Issue: 1 Pages: 14585-14585

    • DOI

      10.1038/ncomms14585

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Germline recombination in a novel Cre transgenic line, Prl3b1-cre mouse.2016

    • Author(s)
      Al-Soudy AS, Hiromori Y, Mizuno S, Hasegawa Y, Shawki HH, Katoh MC, Basha WA, Ibrahim AE, El-Shemy HA, Iseki Hi, Yoshiki A, Nagase H, Nakanishi T, Takahashi S, Oishi H, Sugiyama F.
    • Journal Title

      Genesis.

      Volume: 54(7) Issue: 7 Pages: 389-97

    • DOI

      10.1002/dvg.22944

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Ligand Activity of Group 15 Compounds Possessing Triphenyl Substituent for the RXR and PPARγ Nuclear Receptors2016

    • Author(s)
      Youhei Hiromori 他5名
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 39 Issue: 10 Pages: 1596-1603

    • DOI

      10.1248/bpb.b16-00186

    • NAID

      130005598445

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Male Hypogonadism Causes Obesity Associated with Impairment of Hepatic Gluconeogenesis in Mice2016

    • Author(s)
      Akira Aoki 他5名
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 39 Issue: 4 Pages: 587-592

    • DOI

      10.1248/bpb.b15-00942

    • NAID

      130005141675

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transactivation of the human retinoid X receptor by organotins: use of site-directed mutagenesis to identify critical amino acid residues for organotin-induced transactivation.2015

    • Author(s)
      Hiromori Y, Aoki A, Nishikawa J, Nagase H, Nakanishi T.
    • Journal Title

      Metallomics

      Volume: 7 Issue: 7 Pages: 1180-1188

    • DOI

      10.1039/c5mt00086f

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Structure-dependent activity of phthalate esters and phthalate monoesters binding to human constitutive androstane receptor.2015

    • Author(s)
      Zhang H, Zhang Z, Nakanishi T, Wan Y, Hiromori Y, Nagase H, Hu J.
    • Journal Title

      Chemical Research in Toxicology

      Volume: 28 Issue: 6 Pages: 1196-1204

    • DOI

      10.1021/acs.chemrestox.5b00028

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Structural basis for PPARgamma transactivation by endocrine disrupting organotin compounds.2015

    • Author(s)
      Harada, S., Hiromori, Y., Nakamura, S., Kawahara, K., Fukakusa, S., Maruno, T., Noda, M., Uchiyama, S., Fukui, K., Nishikawa, J., Nagase, H., Kobayashi, Y., Yoshida, T., Ohkubo, T., Nakanishi, T.,
    • Journal Title

      Sci. Rep.

      Volume: 5:8520 Issue: 1 Pages: 1-7

    • DOI

      10.1038/srep08520

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Organotin compounds cause structure-dependent induction of progesterone in human choriocarcinoma Jar cells.2015

    • Author(s)
      Hiromori Y, Yui H, Nishikawa JI, Nagase H, Nakanishi T
    • Journal Title

      The Journal of Steroid Biochemistry and Molecular Biology

      Volume: in press Pages: 190-198

    • DOI

      10.1016/j.jsbmb.2014.10.010

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gene expression differences in the duodenum of 129/Sv and DBA/2 mice compared with that of C57BL/6J mice2014

    • Author(s)
      Imai S, Tokumoto M, Fujiwara Y, Honda A, Hasegawa T, Seko Y, Lee JY, Nagase H, Satoh M
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 39 Issue: 1 Pages: 173-177

    • DOI

      10.2131/jts.39.173

    • NAID

      130004447110

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A mollusk retinoic acid receptor (RAR) ortholog sheds light on the evolution of ligand binding2014

    • Author(s)
      Gutierrez-Mazariegos J, Kumar Nadendla E, Lima D, Kane M, Nishikawa J, Hiromori Y, Nakanishi T, Santos MM, Castro LFC, Bourguet W, Schubert M, Laudet V
    • Journal Title

      Endocrinology

      Volume: 155 Issue: 11 Pages: 4275-4286

    • DOI

      10.1210/en.2014-1181

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Microarray analysis of neonatal brain exposed to cadmium during gestation and lactation2013

    • Author(s)
      Akiko Honda 他4名
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 38 Issue: 1 Pages: 151-153

    • DOI

      10.2131/jts.38.151

    • NAID

      10031138737

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] in vivoイメージングを用いたエストロゲン作動性スクリーニング試験法の構築2017

    • Author(s)
      中西 剛
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台市
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] エストロゲン応答性レポーターマウスを用いたin vivoエストロゲン作動性スクリーニング試験法の構築2016

    • Author(s)
      古川誠之 他4名
    • Organizer
      フォーラム2016:衛生薬学・環境トキシコロジー
    • Place of Presentation
      東京
    • Year and Date
      2016-09-10
    • Related Report
      2016 Annual Research Report
  • [Presentation] 胎盤内分泌機能に対するプロポリスの影響およびその分子機構に関する検討2016

    • Author(s)
      荒川脩平 他4名
    • Organizer
      フォーラム2016:衛生薬学・環境トキシコロジー
    • Place of Presentation
      東京
    • Year and Date
      2016-09-10
    • Related Report
      2016 Annual Research Report
  • [Presentation] Development of novel in vivo estrogen-like effects screening assay using estrogen reporter "E-Rep" mice2016

    • Author(s)
      Motoshi Furukawa 他5名
    • Organizer
      2016 ICCA-LRI & NIHS Workshop
    • Place of Presentation
      Awaji
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マウス子宮におけるトリフェニルスズのエストロゲンシグナル増強作用2016

    • Author(s)
      松田健志 他3名
    • Organizer
      第43回日本毒性学会学術年会
    • Place of Presentation
      名古屋市
    • Related Report
      2016 Annual Research Report
  • [Presentation] 外生殖器形成における胎生期エストロゲン作用の生理的意義の解明2016

    • Author(s)
      玉井一輝 他3名
    • Organizer
      日本病院薬剤師会東海ブロック・日本薬学会東海支部合同学術大会2016
    • Place of Presentation
      岐阜市
    • Related Report
      2016 Annual Research Report
  • [Presentation] 有機スズ化合物およびレチノイドのRXR 転写活性化における必須アミノ酸部位の検討2015

    • Author(s)
      廣森洋平 他4名
    • Organizer
      日本病院薬剤師会東海ブロック・日本薬学会東海支部 合同学術大会2015
    • Place of Presentation
      名古屋市
    • Year and Date
      2015-11-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] 抗アンドロゲン剤ばく露による肝臓の糖代謝異常を伴う脂肪蓄積の亢進2015

    • Author(s)
      髙木康平 他4名
    • Organizer
      フォーラム2015:衛生薬学・環境トキシコロジー
    • Place of Presentation
      神戸市
    • Year and Date
      2015-09-17
    • Related Report
      2015 Annual Research Report
  • [Presentation] Anti-androgenic effects induce obesity associated with impairment of hepatic gluconeogesis in mice2015

    • Author(s)
      Akira Aoki 他3名
    • Organizer
      51st Congress of the European Societies of Toxicology
    • Place of Presentation
      Porto, Portugal
    • Year and Date
      2015-09-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 有機スズ化合物およびレチノイドの RXR 転写活性化における必須アミノ酸部位の検討2015

    • Author(s)
      廣森洋平 他6名
    • Organizer
      第10回メタルバイオサイエンス研究会
    • Place of Presentation
      名古屋市
    • Year and Date
      2015-08-27
    • Related Report
      2015 Annual Research Report
  • [Presentation] 有機スズ化合物とヒトPPARgammaの結合様式の解明2015

    • Author(s)
      中西 剛 他6名
    • Organizer
      第26回日本微量元素学会学術集会
    • Place of Presentation
      札幌市
    • Year and Date
      2015-07-04
    • Related Report
      2015 Annual Research Report
  • [Presentation] ヒト胎盤における有機スズ化合物のプロゲステロン産生への影響2015

    • Author(s)
      廣森洋平 他3名
    • Organizer
      第61 回日本薬学会東海支部 総会・大会
    • Place of Presentation
      名古屋市
    • Year and Date
      2015-07-04
    • Related Report
      2015 Annual Research Report
  • [Presentation] 有機スズの核内受容体を介した免疫抑制作用2015

    • Author(s)
      中西 剛
    • Organizer
      第42回日本毒性学会学術年会
    • Place of Presentation
      金沢市
    • Year and Date
      2015-07-01
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Organtoin-induced endocrine disruption in human placenta via nuclear receptor signaling2015

    • Author(s)
      Tsuyoshi Nakanishi
    • Organizer
      The 7th International Congress of Asian Society of Toxicology (ASIATOX2015)
    • Place of Presentation
      済州島,韓国
    • Year and Date
      2015-06-24
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 成熟期マウスの性腺機能によるトリフェニルスズの毒性発現性修飾2015

    • Author(s)
      松田健志、大塚佑基、青木 明、中西 剛、永瀬久光
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸学院大学(兵庫県神戸市)
    • Year and Date
      2015-03-25 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] 卵巣機能によるTPT毒性発現修飾2014

    • Author(s)
      大塚佑基、青木 明、中西 剛、永瀬久光
    • Organizer
      第4回メタロミクス研究フォーラム
    • Place of Presentation
      武蔵野大学(東京都西東京市)
    • Year and Date
      2014-11-07 – 2014-11-08
    • Related Report
      2014 Annual Research Report
  • [Presentation] In vivo profiling of potential Estrogenic Action induced by Royal Jelly in Female using Estrogen Reporter (E-Rep) mice2014

    • Author(s)
      Nakanishi T
    • Organizer
      The First Congress of the International Federation of Apitherapy and the VII-th. of the Romanian Apitherapy Society
    • Place of Presentation
      Brasov, Romania
    • Year and Date
      2014-10-17 – 2014-10-21
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 有機スズ化合物の毒性発現に対するMajor Urinary Protein1の影響2014

    • Author(s)
      青木 明、大塚佑基、中西 剛、永瀬久光
    • Organizer
      フォーラム2014:衛生薬学・環境トキシコロジー
    • Place of Presentation
      つくば国際会議場(茨城県つくば市)
    • Year and Date
      2014-09-19 – 2014-09-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] トリフェニルスズの全身免疫系に対する加齢化促進作用の検討2014

    • Author(s)
      廣森洋平、酒井紀行、小林 亮、上代大地、中西 剛、永瀬 久光
    • Organizer
      第21回日本免疫毒性学会学術年会
    • Place of Presentation
      徳島文理大学(徳島県徳島市)
    • Year and Date
      2014-09-11 – 2014-09-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Organotin compounds cause structure-dependent induction of progesterone in human choriocarcinoma Jar cells2014

    • Author(s)
      Nakanishi T, Hiromori Y, Nishikawa J, Nagase H
    • Organizer
      EuroTox 2014: 50th Congress of the European Societies of Toxicology
    • Place of Presentation
      Edinburgh, UK
    • Year and Date
      2014-09-07 – 2014-09-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] TPTの成熟期雌性マウスにおける28日間反復経口投与毒性試験と卵巣機能による毒性発現修飾2014

    • Author(s)
      青木 明、大塚佑基、中西 剛、永瀬久光
    • Organizer
      第25回日本微量元素学会学術集会
    • Place of Presentation
      岡山大学創立五十周年記念館(岡山県岡山市)
    • Year and Date
      2014-07-03 – 2014-07-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] 脳の性分化と胎生期エストロゲンシグナル2014

    • Author(s)
      中西 剛
    • Organizer
      第41回日本毒性学会学術年会
    • Place of Presentation
      神戸コンベンションセンター(兵庫県神戸市)
    • Year and Date
      2014-07-02 – 2014-07-04
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 核内受容体を介した有機スズ化合物の毒性2014

    • Author(s)
      廣森洋平、中西 剛、永瀬久光
    • Organizer
      第41回日本毒性学会学術年会
    • Place of Presentation
      神戸コンベンションセンター(兵庫県神戸市)
    • Year and Date
      2014-07-02 – 2014-07-04
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 酵母 two-hybrid 法を用いたヒトおよびマウスPXRアゴニスト活性評価系の構築2014

    • Author(s)
      桑山 隼、廣森洋平、西川淳一、中西 剛、永瀬久光
    • Organizer
      第41回 日本毒性学会学術年会
    • Place of Presentation
      神戸コンベンションセンター(兵庫県神戸市)
    • Year and Date
      2014-07-02 – 2014-07-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] The Roles of Major Urinary Protein 1 As a Regulator for Adipocyte Differentiation in Mice2014

    • Author(s)
      Aoki A, Nagase H and Nakanishi T
    • Organizer
      16th International Congress of Endocrinology & the Endocrine Society’s 96th Annual Meeting & Expo
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2014-06-21 – 2014-06-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] アンドロゲンはどこまで性分化を制御できるのか?-化学物質の抗アンドロゲン作用評価系構築に向けて-2014

    • Author(s)
      西岡 康 他3名
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本大学(熊本)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] エストロゲン応答性レポーターマウスを用いたローヤルゼリーのエストロゲン活性評価2013

    • Author(s)
      志水真也 他4名
    • Organizer
      第40回日本毒性学会学術年会
    • Place of Presentation
      幕張メッセ(千葉)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Diethylstilbestrolの蓄積性とエストロゲンシグナルかく乱作用2013

    • Author(s)
      松田達也 他4名
    • Organizer
      第40回日本毒性学会学術年会
    • Place of Presentation
      幕張メッセ(千葉)
    • Related Report
      2013 Annual Research Report
  • [Presentation] In vivo profiling of 2,3,7,8-tetrachrolodibenzo-p-dioxin-induced estrogenic/anti-estrogenic action in female using estrogen reporter (E-Rep) mice2013

    • Author(s)
      Tsuyoshi Nakanishi 他4名
    • Organizer
      International Congress of Toxicology 2013
    • Place of Presentation
      COEX(Seoul)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Possible aryl hydrocarbon receptor-independent pathway 2,3,7,8-tetrachlorodibenzo-p-dioxin -induced antiproliferative response in human breast cancer MCF-7 cells2013

    • Author(s)
      Hiroki Yoshioka 他6名
    • Organizer
      International Congress of Toxicology 2013
    • Place of Presentation
      COEX(Seoul)
    • Related Report
      2013 Annual Research Report
  • [Presentation] アンドロゲン高産生マウスにおける生殖器形成の解析(第1報)~胎生期の検討~2013

    • Author(s)
      伊師賢樹 他3名
    • Organizer
      第53回日本先天異常学会学術集会
    • Place of Presentation
      千里ライフサイエンスセンター(大阪)
    • Related Report
      2013 Annual Research Report
  • [Presentation] アンドロゲン高産生マウスにおける生殖器形成の解析(第2報)~出生後の検討~2013

    • Author(s)
      西岡 康 他3名
    • Organizer
      第53回日本先天異常学会学術集会
    • Place of Presentation
      千里ライフサイエンスセンター(大阪)
    • Related Report
      2013 Annual Research Report
  • [Presentation] エストロゲン応答性レポーターマウスを用いたローヤルゼリーのエストロゲン活性評価2013

    • Author(s)
      志水真也 他4名
    • Organizer
      フォーラム2013 衛生薬学・環境トキシコロジー
    • Place of Presentation
      九州大学(福岡)
    • Related Report
      2013 Annual Research Report
  • [Presentation] アンドロゲン高産生マウスを用いた胎生期生殖器形成の解析2013

    • Author(s)
      伊師賢樹 他3名
    • Organizer
      フォーラム2013 衛生薬学・環境トキシコロジー
    • Place of Presentation
      九州大学(福岡)
    • Related Report
      2013 Annual Research Report
  • [Presentation] アンドロゲンの糖・脂質代謝制御におけるリポカリンファミリー分子MUP1の役割2013

    • Author(s)
      藤谷航平 他4名
    • Organizer
      フォーラム2013 衛生薬学・環境トキシコロジー
    • Place of Presentation
      九州大学(福岡)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 胎生期エストロゲンシグナルと性分化2013

    • Author(s)
      中西 剛
    • Organizer
      第32回関西生殖発生毒性フォーラム
    • Place of Presentation
      明治安田生命大阪御堂筋ビル(大阪)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 高感度in vivoエストロゲン活性評価系の構築とローヤルゼリーのエストロゲン活性評価2013

    • Author(s)
      志水真也 他4名
    • Organizer
      第4回岐阜薬科大学機能性健康食品(蜂産品)研究講演会
    • Place of Presentation
      グランヴェール岐山(岐阜)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 胎仔におけるdiethylstilbestrolの蓄積性とエストロゲンシグナルかく乱作用2013

    • Author(s)
      中西 剛 他3名
    • Organizer
      第18回日本生殖内分泌学会学術集会
    • Place of Presentation
      シェーンバッハ・サボー(東京)
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-21   Modified: 2019-07-29  

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