New concept " Subclnical central hypothyroidism"

• Project/Area Number: 23591345
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Gunma University
• Principal Investigator: YAMADA Masasnobu 群馬大学, 医学(系)研究科(研究院), 教授 (90261833)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 中枢性甲状腺機能低下症 / TRH / TSH / NR4A1 / レプチン / 潜在性内分泌代謝病

Research Abstract

Subclinical hypothyroidism (SCH) is defined as elevated serum thyrotropin (TSH) in the presence of a normal thyroid hormone concentration. Central hypothyroidism (CH) is defined as hypothyroidism due to insufficient stimulation of the thyroid grand by TSH, for which secretion and activity can be impaired at either the hypothalamic or pituitary level. In the present study, we found a new clinical concept"subclinical central hypothyroidism" and investigated its pathophysiology using TRH knockout mice.

Research Products

• [Journal Article] Hypothalamic SIRT1 prevents age-associated weight gain by improving leptin sensitivity in mice. (2014)
  • Author(s): Sasaki T, Kikuchi O, Shimpuku M, Susanti VY, Yokota-Hashimoto H, Taguchi R, Shibusawa N, Sato T, Tang L, Amano K, Kitazumi T, Kuroko M, Fujita Y, Maruyama J, Lee YS, Kobayashi M, Nakagawa T, Minokoshi Y, Harada A, Yamada M, Kitamura T.
  • Journal Title: Diabetologia Volume: 57 Issue: 4 Pages: 819-831
  • DOI: 10.1007/s00125-013-3140-5
  • Peer Reviewed / Open Access
• [Journal Article] Subclinical hypothyroidism and indices for metabolic syndrome in Japanese women:one-year follw-up study (2013)
  • Author(s): Nakajima Y, Yamada M, Akuzawa M, Ishii S, Masamura Y, Satoh T, Hashimoto K, Negishi M, Shimomura Y, Kobayashi I, Andou Y, Mori M
  • Journal Title: J Clin Endocrinol Metab Volume: 98 Issue: 8 Pages: 3280-3287
  • DOI: 10.1210/jc.2013-1353
  • Peer Reviewed
• [Journal Article] THRAP3 interacts with HELZ2 and plays a novel role in adipocyte differentiation. (2013)
  • Author(s): Katano-Toki A, Satoh T, Tomaru T, Yoshino S, Ishizuka T, Ishii S, Ozawa A, Shibusawa N, Tsuchiya T, Saito T, Shimizu H, Hashimoto K, Okada S, Yamada M, Mori M
  • Journal Title: Molecular Endocrinology Volume: 27 Issue: 5 Pages: 769-780
  • DOI: 10.1210/me.2012-1332
  • Peer Reviewed
• [Journal Article] KCNJ5 mutations in aldosterone- and cortisol-co-secreting adrenal adenomas (2012)
  • Author(s): Yamada M, Nakajima Y, Taguchi R, Okamura T, Ishii S, Tomaru T, Ozawa A, Shibusawa N, Yoshino S, Toki A, Ishida E, Hashimoto K, Satoh T, Mori M
  • Journal Title: Endocr J Volume: 59 Pages: 735-741
  • NAID: 10031064823
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/22863749
  • Peer Reviewed
• [Journal Article] NR4A1 (Nur77) mediates thyrotropin-releasing hormone-induced stimulation of transcription of the thyrotropin β gene: analysis of TRH knockout mice. (2012)
  • Author(s): Nakajima Y
  • Journal Title: PLos One Volume: 7 Issue: 7 Pages: e40437-e40437
  • DOI: 10.1371/journal.pone.0040437
  • Peer Reviewed
• [Journal Article] Expression of mutations of KCNJ5 mRNA in Japanese patients with aldosterone-producing adenomas. (2012)
  • Author(s): Taguchi R
  • Journal Title: J Clin Endocrinol Metab Volume: 97 Issue: 4 Pages: 1311-1319
  • DOI: 10.1210/jc.2011-2885
  • Peer Reviewed
• [Journal Article] Haploinsufficient and Predominant Expression of Multiple Endocrine Neoplasia Type 1 (MEN1)-Related Genes, MLL, p27^<Kip1>and p18^<Ink4C>in Endocrine Organs (2011)
  • Author(s): Taguchi R, Yamada M, Horiguchi K, Ozawa A, Shibusawa N, Hashimoto K, Satoh T, Mori M
  • Journal Title: Biochem Biophys Res Commun Volume: 415 Issue: 2 Pages: 378-383
  • DOI: 10.1016/j.bbrc.2011.10.077
  • Peer Reviewed
• [Journal Article] Cardiovascular complications of patients with aldosteronism associated with autonomous cortisol secretion (2011)
  • Author(s): Nakajima Y, Yamada M, Taguchi R, Satoh T, Hashimoto K, Ozawa A, Shibusawa N, Okada S, Monden T, Mori M
  • Journal Title: J Clin Endocrinol Metab Volume: 96 Issue: 8 Pages: 2512-2518
  • DOI: 10.1210/jc.2010-2743
  • Peer Reviewed
• [Journal Article] Attenuated expression of menin and p27 (Kip1) in an aggressive case of multiple endocrine neoplasia type 1 (MEN1) associated with an atypical prolactinoma and a malignant pancreatic endocrine tumor (2011)
  • Author(s): Ishida E, Yamada M, Horiguchi K, Taguchi R, Ozawa A, Shibusawa N, Hashimoto K, Satoh T, Yoshida S, Tanaka Y, Yokota M, Tosaka M, Hirato J, Yamada S, Yoshimoto Y, Mori M
  • Journal Title: Endocr J Volume: 58 Pages: 287-296
  • NAID: 130004443685
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/21441703
  • Peer Reviewed
• [Journal Article] Liver X receptor-α/βexpression ratio is increased in ACTH-secreting pituitary adenomas (2011)
  • Author(s): Hashimoto K, Matsumoto S, Ishida E, Miura A, Horiguchi K, Ozawa A, Shibusawa N, Satoh T, Yamada M, Yamada S, Mori M
  • Journal Title: Neurosci Lett Volume: 494 Pages: 34-37
  • Peer Reviewed
• [Journal Article] Attenuated expression of menin and p27 (Kip1) in an aggressive case of multiple endocrine neoplasia type 1 (MEN1) associated with an atypical prolactinoma and a malignant pancreatic endocrine tumor. (2011)
  • Author(s): 6.Ishida E, Yamada M, Horiguchi K, Taguchi R, Ozawa A, Shibusawa N, Hashimoto K, Satoh T, Yoshida S, Tanaka Y, Yokota M, Tosaka M, Hirato J, Yamada S, Yoshimoto Y, Mori M.
  • Journal Title: Endocr J. Volume: 58 Pages: 287-296
  • NAID: 130004443685
  • Peer Reviewed
• [Presentation] 視床下部TRHの下垂体TSH分泌並びに発現制御機構 (2014)
  • Author(s): 中島康代、岡本孝志、渋沢信行、小澤厚志、堀口和彦、橋本貢士、佐藤哲郎、佐々木努、北村忠弘、山田正信
  • Organizer: 第87回日本内分泌学会学術集会
  • Place of Presentation: 福岡
  • Invited
• [Presentation] 摂食抑制ペプチドNesfatin-1の細胞内シグナル伝達機構の解析とその特異的受容体の探索 (2013)
  • Author(s): 橋本貢士,石田恵美,武田茂樹,登丸琢也,石井角保,小澤厚志,渋沢信行,佐藤哲郎,岡田秀一,清水弘行,山田正信,森昌朋
  • Organizer: 第86回日本内分泌学会
  • Place of Presentation: 仙台
  • Year and Date: 2013-04-25
• [Presentation] 甲状腺刺激ホルモン放出ホルモンによる膵島FGF21遺伝子発現調節機構 (2012)
  • Author(s): 渋沢信行,田口亮,登丸琢也,石井角保,小澤厚志,橋本貢士,佐藤哲郎,山田正信,森昌朋
  • Organizer: 第55回日本甲状腺学会
  • Place of Presentation: 福岡
  • Year and Date: 2012-11-29
• [Presentation] 下垂体NR4A1(Nur77)を介する視床下部-下垂体-甲状腺系のエネルギー代謝調節機構 (2012)
  • Author(s): 山田正信,渋澤信行,田口亮,中島康代,橋本貢士,佐藤哲郎,森昌朋
  • Organizer: 第33回日本肥満学会
  • Place of Presentation: 京都
  • Year and Date: 2012-10-11
• [Presentation] 下垂体前葉疾患の研究の進歩潜在性内分泌代謝病をリードする甲状腺機能異常の多様性 (2012)
  • Author(s): 山田正信,田口亮,堀口和彦,中島康代,佐藤哲朗,橋本貢士,山崎勇一,柿崎暁,登坂雅彦,好本裕平,山田正三,森昌朋
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2012-04-21
• [Presentation] 下垂体の機能調節に関わる新規分子の解明TRHノックアウトマウスを用いた新たな生理活性経路の探索 (2012)
  • Author(s): 山田正信,中島康代,田口亮,森昌朋
  • Organizer: 第89回日本生理学会大会
  • Place of Presentation: 松本(シンポジウム)
  • Year and Date: 2012-03-30
• [Presentation] 下垂体の機能調節に関わる新規分子の解明TRHノックアウトマウスを用いた新たな生理活性経路の探索 (2012)
  • Author(s): 山田正信, 中島康代, 田口亮, 森昌朋
  • Organizer: 第８９回日本生理学会大会
  • Place of Presentation: 松本
  • Invited
• [Presentation] 変異JunDによる膵内分泌腫瘍発症機構:マウスモデルの解析 (2011)
  • Author(s): 小澤厚志,山田正信,田口亮,登丸琢也,渋沢信行,橋本貢士,佐藤哲郎,森昌朋
  • Organizer: 第38回日本神経内分泌学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2011-11-26
• [Presentation] レプチンの視床下部―下垂体―甲状腺系制御機構:TRHノックアウトマウス(TRHKO)の解析 (2011)
  • Author(s): 山田正信,田口亮,中島康代,渋沢信行,Garay Guerrero J,小澤厚志,橋本貢士,佐藤哲郎,森昌朋
  • Organizer: 第32回日本肥満学会学術集会
  • Place of Presentation: 淡路
  • Year and Date: 2011-09-23
• [Presentation] MEN1遺伝子変異陰性例におけるp27ならびにp18遺伝子の意義:悪性度の高いMENI症例における特徴から (2011)
  • Author(s): 山田正信,小澤厚志,田口亮,石田恵美,森昌朋,梶博史,今井常夫,櫻井晃洋
  • Organizer: 第17回日本家族性腫瘍学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2011-06-17
• [Presentation] レプチンのTRH-TSH-甲状腺系制御機構 (2011)
  • Author(s): 山田正信,田口亮,Garay Guerrero J,小澤厚志,渋沢信行,橋本貢士,佐藤哲郎,森昌朋
  • Organizer: 第54回日本糖尿病学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2011-05-19
• [Presentation] 本邦の多発性内分泌腺腫症I型におけるMEN1遺伝子変異陰性例の特徴p27並びにp18遺伝子変異の検討 (2011)
  • Author(s): 山田正信,小澤厚志,田口亮,梶博史,今井常夫,櫻井晃洋
  • Organizer: 第84回日本内分泌学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2011-04-21
• [Presentation] TRHノックアウトマウスを用いた新たな生理活性経路の探索
  • Author(s): 山田正信、中島康代、田口亮、森昌朋
  • Organizer: 第８９回日本生理学会大会(招待講演)
  • Place of Presentation: 長野県松本文化会館