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Investigation for molecular basis of hypothalamo-pituitary-gonadal dysfunction

Research Project

Project/Area Number 23390249
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionNational Research Institute for Child Health and Development

Principal Investigator

FUKAMI MAKI  独立行政法人国立成育医療研究センター, その他部局等, その他 (40265872)

Co-Investigator(Kenkyū-buntansha) SONEDA Shun  独立行政法人国立成育医療研究センター, 分子内分泌研究部, 研究員 (10367378)
KATO Fumiko  浜松医科大学, 小児科, 研究員 (10462798)
Project Period (FY) 2011-11-18 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
Fiscal Year 2013: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2012: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Keywords遺伝子 / ホルモン / 先天疾患 / 性分化 / 小児内分泌学
Research Abstract

The aim of the present study was to clarify the molecular basis of reproduction failure. We performed systematic mutation screening and genome-wide copy number analyses for patients with disorders of sex development (DSD), gonadotropin deficiency, and precocious puberty. Our results include; 1) Mutations in known causative genes account for only a small fraction of the etiology of 46,XY DSD and gonadotropin deficiency. 2) FGF8 haploinsufficiency may underlie thyroid dysfunction and cardiac anomalies. 3) Cryptic genomic rearrangements constitute rare causes of 46,XY, DSD. 4) Genomic rearrangements leading to aromatase excess syndrome (AEXS) are caused by recombination- and replication-based mechanisms. 5) Hypogonadism in patients with AEXS is ascribed to the negative-feedback effect of estrogens on FSH secretion. 6) Adrenal androgens serve as the major source of estrogens in prepubertal patients with AEXS. 7) SOX2 mutations are associated with a broad phenotypic variation.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (56 results)

All 2014 2013 2012 Other

All Journal Article (17 results) (of which Peer Reviewed: 13 results) Presentation (32 results) (of which Invited: 12 results) Remarks (7 results)

  • [Journal Article] Lack of genomic rearrangements involving the aromatase gene CYP19A1 in breast cancer.2014

    • Author(s)
      Fukami M*, Suzuki J, Nakabayashi K, Tsunashima R, Ogata T, Shozu M, Noguchi S
    • Journal Title

      Breast Cancer

      Volume: 21 (3) Issue: 3 Pages: 382-385

    • DOI

      10.1007/s12282-013-0471-5

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Birth seasonality in Prader-Willi syndrome resulting from chromosome 15 microdeletion.2013

    • Author(s)
      Ayabe T, Matsubara K, Ogata T, Ayabe A, Murakami N, Nagai T, Fukami M*
    • Journal Title

      Am J Med Genet A

      Volume: 161 Issue: 6 Pages: 1495-1497

    • DOI

      10.1002/ajmg.a.35893

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Submicroscopic deletion involving the fibroblast growth factor receptor 1 gene in a patient with combined pituitary hormone deficiency2013

    • Author(s)
      Fukami M, Iso M, Sato N, Igarashi M, Seo M, Kazukawa I, Kinoshita E, Dateki S, Ogata T
    • Journal Title

      Endocr J

      Volume: 60(8) Pages: 1013-1020

    • NAID

      10031195771

    • Related Report
      2013 Final Research Report
  • [Journal Article] Human glutathione S-transferase A (GSTA) family genes are regulated by steroidogenic factor 1 (SF-1) and are involved in steroidogenesis.2013

    • Author(s)
      Matsumura T, Imamichi Y, Mizutani T, Ju Y, Yazawa T, Kawabe S, Kanno M, Ayabe T, Katsumata N, Fukami M, Inatani M, Akagi Y, Umezawa A, Ogata T, Miyamoto K
    • Journal Title

      FASEB J

      Volume: 27 Issue: 8 Pages: 3198-3208

    • DOI

      10.1096/fj.12-222745

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A 68-year-old phenotypically male patient with 21 -hydroxylase deficiency and concomitant adrenocortical neoplasm producing testosterone and cortisol2013

    • Author(s)
      Hayashi M, Kataoka Y, Sugimura Y, Kato F, Fukami M, Ogata T, Homma K, Hasegawa T, Oiso Y, Sasano H, Tanaka H
    • Journal Title

      Tohoku J Exp Med

      Volume: 231 (2) Pages: 75-84

    • NAID

      130004720753

    • Related Report
      2013 Final Research Report
  • [Journal Article] Cryptic genomic rearrangements in three patients with 46,XY disorders of sex development2013

    • Author(s)
      M. Igarashi, V. C. Dung, E. Suzuki, S. Ida, M. Nakacho, K. Nakabayashi, K. Mizuno, Y. Hayashi, K. Kohri, Y. Kojima, T. Ogata, M. Fukami
    • Journal Title

      PLoS. One

      Volume: 8 Issue: 7 Pages: e68194-e68194

    • DOI

      10.1371/journal.pone.0068194

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genomic basis of aromatase excess syndrome: recombination- and replication-mediated rearrangements leading to CYP19A1 overexpression.2013

    • Author(s)
      Fukami M*, Tsuchiya T, Vollbach H, Brown KA, Abe S, Ohtsu S, Wabitsch M, Gurger H, Sompson ER, Emezawa A, Nakabayashi K, Bulun SE, Shozu M, Ogata T
    • Journal Title

      J Clin Endocrinol Metab

      Volume: 98 Issue: 12 Pages: E2013-E2021

    • DOI

      10.1210/jc.2013-2520

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Aromatase excess syndrome in a family with upstream deletion of CYP19A12013

    • Author(s)
      Shihara D, Miyado M, Nakabayashi K, Shozu M, Nagasaki K, Ogata T, Fukami M*
    • Journal Title

      Clin Endocrinol,

      Volume: Epub ahead of print Issue: 2 Pages: 314-316

    • DOI

      10.1111/cen.12329

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A 68-year-old phenotypically male patient with 21-hydroxylase deficiency and concomitant adrenocortical neoplasm producing testosterone and cortisol.2013

    • Author(s)
      Hayashi M, Kataoka Y, Sugimura Y, Kato F, Fukami M, Ogata T, Homma K, Hasegawa T, Oiso Y, Sasano H, Tanaka H
    • Journal Title

      Tohoku J Exp Med.

      Volume: 231

    • NAID

      130004720753

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Birth Seasonality in Prader-Willi Syndrome Resulting from Chromosome 15 Microdeletion.2013

    • Author(s)
      Ayabe T, Matsubara K. Ogata T, Ayabe A, Murakami N, Nagai T, Fukami M.
    • Journal Title

      Am J Med Genet A.

      Volume: 未定

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Submicroscopic deletion involving the fibroblast growth factor receptor 1 gene in a patient with combined pituitary hormone deficiency2013

    • Author(s)
      Fukami M, Iso M, Sato N, Igarashi M, Seo M, Kazukawa I, Kinoshita E, Dateki S,Ogata T.
    • Journal Title

      Endocrine J

      Volume: 未定

    • NAID

      10031195771

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lack of Genomic Rearrangements Involving the Aromatase Gene CYP19A1 in Breast Cancer2013

    • Author(s)
      Fukami M, Suzuki J, Nakabayashi K, Tsunasima R, Ogata T, Shozu M, Noguchi S.
    • Journal Title

      Breast cancer

      Volume: 未定

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Complex genomic rearrangements in the SOX9 5' region in a patient with Pierre Robin sequence and hypoplastic left scapula.2012

    • Author(s)
      M. Fukami, T. Tsuchiya, S. Takada, A. Kanbara, H. Asahara, A. Igarashi, Y. Kamiyama, G. Nishimura, T. Ogata.
    • Journal Title

      Am. J. Med. Genet. A.

      Volume: 158A Issue: 7 Pages: 1529-1534

    • DOI

      10.1002/ajmg.a.35308

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PRKAR1A mutation affecting cAMP-mediated G-protein-coupled receptor signaling in a patient with acrodysostosis and hormone resistance2012

    • Author(s)
      Nagasaki K, Iida T, Sato H, Ogawa Y, Kikuchi T, Saitoh A, Ogata T, Fukami M
    • Journal Title

      J Clin Endocrinol Metab

      Volume: 97(9) Issue: 9 Pages: E1808-E1813

    • DOI

      10.1210/jc.2012-1369

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mamld1 deficiency significantly reduces mRNA expression levels of multiple genes expressed in mouse fetal Leydig cells but permits normal genital and reproductive development2012

    • Author(s)
      Miyado M, Nakamura M, Miyado K, Morohashi K, Sano S, Nagata E, Fukami M, Ogata T
    • Journal Title

      Endocrinology

      Volume: 153(12) Issue: 12 Pages: 6033-6040

    • DOI

      10.1210/en.2012-1324

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] アロマターゼ過剰症候群内科2012

    • Author(s)
      深見真紀
    • Journal Title

      1 09 (6

      Volume: 109 (6)

    • Related Report
      2013 Final Research Report
  • [Journal Article] アロマターゼ過剰症候群2012

    • Author(s)
      深見真紀
    • Journal Title

      内科

      Volume: 109(印刷中)

    • Related Report
      2011 Annual Research Report
  • [Presentation] 性分化疾患の遺伝子診断2014

    • Author(s)
      深見真紀
    • Organizer
      第23回臨床内分泌代謝Update
    • Place of Presentation
      名古屋
    • Year and Date
      2014-01-25
    • Related Report
      2013 Final Research Report
  • [Presentation] POR欠損症の分子基盤と臨床像2013

    • Author(s)
      深見真紀
    • Organizer
      第21回日本ステロイドホルモン学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2013-11-16
    • Related Report
      2013 Final Research Report
  • [Presentation] 小児内分泌疾患の遺伝子解析 : 新規解析技術を用いた疾患成立機序の解明2013

    • Author(s)
      深見真紀
    • Organizer
      第22回小児内分泌代謝フォーラムin九州
    • Place of Presentation
      福岡
    • Year and Date
      2013-07-27
    • Related Report
      2013 Final Research Report
  • [Presentation] Molecular diagnosis and management of hereditary gynecomastia. In : Meet-the-expert session2013

    • Author(s)
      Fukami M
    • Organizer
      The 9th Joint meeting of pediatric endocrinology
    • Place of Presentation
      Milan
    • Related Report
      2013 Final Research Report
  • [Presentation] 内分泌疾患のゲノムコピー数解析2013

    • Author(s)
      深見真紀
    • Organizer
      第86回日本内分泌学会学術総会シンポジウム
    • Place of Presentation
      仙台
    • Related Report
      2013 Final Research Report
  • [Presentation] 新規遺伝子解析技術を用いたヒト性分化疾患・性成熟疾患の病因解析2013

    • Author(s)
      深見真紀
    • Organizer
      日本アンドロロジー学会第32回学術大会
    • Place of Presentation
      大阪
    • Related Report
      2013 Final Research Report
  • [Presentation] Molecular diagnosis and management of hereditary gynecomastia.2013

    • Author(s)
      Fukami M
    • Organizer
      The 9th Joint meeting of pediatric endocrinology,
    • Place of Presentation
      Milan
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 内分泌疾患のゲノムコピー数解析2013

    • Author(s)
      深見真紀
    • Organizer
      第86回日本内分泌学会学術総会 シンポジウム
    • Place of Presentation
      仙台
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] POR異常症とは2012

    • Author(s)
      深見真紀
    • Organizer
      第12回大阪小児内分泌勉強会
    • Place of Presentation
      大阪
    • Year and Date
      2012-11-22
    • Related Report
      2013 Final Research Report
  • [Presentation] アロマターゼ過剰症とゴナドトロピン分泌2012

    • Author(s)
      深見真紀
    • Organizer
      日本内分泌学会シンポジウム
    • Place of Presentation
      名古屋
    • Year and Date
      2012-06-26
    • Related Report
      2013 Final Research Report 2011 Annual Research Report
  • [Presentation] Aromatase Excess Syndrome : Molecular Basis and Phenotypic Determinants. In : Topic Symposium2012

    • Author(s)
      Fukami M
    • Organizer
      Annual Meeting of Pediatric Academic Societies
    • Place of Presentation
      Boston
    • Related Report
      2013 Final Research Report 2011 Annual Research Report
  • [Presentation] 男性における乳房腫大(女性化乳房)2012

    • Author(s)
      深見真紀, 五十嵐麻希, 阿部修司, 山本幸代, 金城さおり , 緒方勤
    • Organizer
      第46回小児内分泌学会とっておきの症例
    • Place of Presentation
      大阪
    • Related Report
      2013 Final Research Report
  • [Presentation] Aromatase Excess Syndrome2012

    • Author(s)
      Fukami M
    • Organizer
      6th International Symposium on the Biology of Vertebrate Sex Determination
    • Place of Presentation
      USA
    • Related Report
      2013 Final Research Report
  • [Presentation] 次世代遺伝子解析技術を用いた性分化疾患141例の病因解析2012

    • Author(s)
      五十嵐麻希, Dung Chi Vu, 小島祥敬, 堀川玲子, 緒方勤, 深見真紀
    • Organizer
      第35回日本分子生物学会ワークショップ
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] Silent mutations of androgen receptor gene in two patients with partial androgen insensitivity syndrome2012

    • Author(s)
      Igarashi M, Kato F, Tsuji Y, Hasegawa Y, Ogata T, Fukami M
    • Organizer
      6th International Symposium on the Biology of Vertebrate Sex Determination
    • Place of Presentation
      USA
    • Related Report
      2013 Final Research Report
  • [Presentation] 精巣における男性ホルモン産生制御機構 : MAMLD1変異陽性患者とノックアウトマウスからの知見2012

    • Author(s)
      宮戸真美, 緒方勤, 深見真紀
    • Organizer
      第35回日本分子生物学会ワークショップ
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] 次世代遺伝子解析技術を用いた性分化疾患141例の病因解析2012

    • Author(s)
      五十嵐麻希, Dung Chi Vu, 小島祥敬, 堀川玲子, 緒方勤, 深見真紀
    • Organizer
      第46回日本小児内分泌学会学術集会
    • Place of Presentation
      大阪
    • Related Report
      2013 Final Research Report
  • [Presentation] 46, XY性分化疾患患者における2番染色体長腕部分欠失の同定2012

    • Author(s)
      鈴木江莉奈, 五十嵐麻希, 宮戸真美, Dung Chi Vu, 緒方勤, 深見真紀
    • Organizer
      第46回日本小児内分泌学会学術集会
    • Place of Presentation
      大阪
    • Related Report
      2013 Final Research Report
  • [Presentation] Aromatase Excess Syndrome: Molecular Basis and Phenotypic Determinants.2012

    • Author(s)
      Fukami M.
    • Organizer
      Annual Meeting of Pediatric Academic Societies
    • Place of Presentation
      Boston, USA
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] アロマターゼ過剰症とゴナドトロピン分泌.2012

    • Author(s)
      深見真紀.
    • Organizer
      日本内分泌学会シンポジウム
    • Place of Presentation
      名古屋
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 男性における乳房腫大(女性化乳房).2012

    • Author(s)
      深見真紀.
    • Organizer
      第46回小児内分泌学会
    • Place of Presentation
      大阪
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] POR異常症とは.2012

    • Author(s)
      深見真紀.
    • Organizer
      第12回大阪小児内分泌勉強会
    • Place of Presentation
      大阪
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 次世代遺伝子解析技術を用いた性分化疾患141例の病因解析.2012

    • Author(s)
      五十嵐麻希,Dung Chi Vu,小島祥敬,堀川玲子,緒方勤,深見真紀.
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Silent mutations of androgen receptor gene in two patients with partial androgen insensitivity syndrome.2012

    • Author(s)
      Igarashi M, Kato F, Tsuji Y, Hasegawa Y, Ogata T, Fukami M.
    • Organizer
      6th International Symposium on the Biology of Vertebrate Sex Determination
    • Place of Presentation
      Kona, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] 精巣における男性ホルモン産生制御機構:MAMLD1変異陽性患者とノックアウトマウスからの知見.2012

    • Author(s)
      宮戸真美,緒方勤,深見真紀
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 次世代遺伝子解析技術を用いた性分化疾患141例の病因解析.2012

    • Author(s)
      五十嵐麻希,Dung Chi Vu,小島祥敬,堀川玲子,緒方勤,深見真紀.
    • Organizer
      第46回日本小児内分泌学会学術集会
    • Place of Presentation
      大阪
    • Related Report
      2012 Annual Research Report
  • [Presentation] 46, XY 性分化疾患患者における2番染色体長腕部分欠失の同定2012

    • Author(s)
      鈴木江莉奈,五十嵐麻希,宮戸真美,Dung Chi Vu,緒方勤,深見真紀.
    • Organizer
      第46回日本小児内分泌学会学術集会
    • Place of Presentation
      大阪
    • Related Report
      2012 Annual Research Report
  • [Presentation] Aromatase Excess Syndrome2012

    • Author(s)
      Fukami M
    • Organizer
      International Symposium on Vertebrate Sex Determination
    • Place of Presentation
      Hawaii
    • Related Report
      2011 Annual Research Report
  • [Presentation] 新規遺伝子解析技術を用いたヒト性分化疾患・性成熟疾患の病因解析

    • Author(s)
      深見真紀
    • Organizer
      日本アンドロロジー学会第32回学術大会.教育講演.
    • Place of Presentation
      大阪
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 小児内分泌疾患の遺伝子解析:新規解析技術を用いた疾患成立機序の解明.

    • Author(s)
      深見真紀
    • Organizer
      第22回小児内分泌代謝フォーラムin九州.
    • Place of Presentation
      福岡
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] POR欠損症の分子基盤と臨床像.

    • Author(s)
      深見真紀
    • Organizer
      第21回日本ステロイドホルモン学会学術集会.シンポジウム
    • Place of Presentation
      大阪
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 性分化疾患の遺伝子診断

    • Author(s)
      深見真紀
    • Organizer
      第23回臨床内分泌代謝Update.シンポジウム
    • Place of Presentation
      名古屋
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Remarks]

    • URL

      http://www.ncchd.go.jp/research.php

    • Related Report
      2013 Final Research Report
  • [Remarks]

    • URL

      http://nch.go.jp/endocrinology/

    • Related Report
      2013 Final Research Report
  • [Remarks] 独立行政法人 国立成育医療研究センター 分子内分泌研究部

    • URL

      http://nrichd.ncchd.go.jp/endocrinology/

    • Related Report
      2013 Annual Research Report
  • [Remarks] 独立行政法人 国立成育医療研究センター 研究所

    • URL

      http://www.ncchd.go.jp/research.php

    • Related Report
      2012 Annual Research Report
  • [Remarks] 独立行政法人 国立成育医療研究センター 分子内分泌研究部

    • URL

      http://nch.go.jp/endocrinology/

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.ncchd.go.jp/research.php

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://111.89.135.117/endocrinology/index.htm

    • Related Report
      2011 Annual Research Report

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Published: 2013-05-15   Modified: 2019-07-29  

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