Identification of molecules affecting ACTH secretion and establishment of novel therapy of pituitary adenomas

2013 Fiscal Year Final Research Report

• Project/Area Number: 23592143
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Teikyo University
• Principal Investigator: MATSUNO AKIRA 帝京大学, 医学部, 教授 (00242058)
• Co-Investigator(Renkei-kenkyūsha): MIZUTANI Akiko 帝京平成大学, 健康メディカル学部, 講師 (80465252) ; TAKEKOSHI Susumu 東海大学, 医学部, 准教授 (70216878) ; OSAMURA Yoshiyuki 国際医療福祉大学, 大学病院健康, 教授 (10100992)
• Project Period (FY): 2011 – 2013
• Keywords: ACTH / 下垂体細胞 / 分泌顆粒

Research Abstract

We focused on adrenocorticotropic hormone and tried to identify and suppress novel molecules playing major roles on formation and intracellular transport of secretory granules. Cells continuously overexpressing ACTH were newly established through transfection to AtT20 cells of GFP-fused wild ACTH and high molecular weight ACTH using episomal vector. Under confocal laser microscopy, intracellular localization of ACTH secretory granules and secretion of ACTH stimulated by CRH and extracellular high potassium were observed. The dynamics of ACTH secretory granules under plasma membrane was also observed under total internal reflection fluorescence microscopy.

Research Products

• [Journal Article] Urinary growth hormone level and insulin-like growth factor-1 standard deviation score (IGF-SDS) can discriminate adult patients with severe growth hormone deficiency (2013)
  • Author(s): Hirohata T, Saito N, Takano K, Yamada S, Son JH, Yamada SM, Nakaguchi H, Hoya K, Murakami M, Mizutani A, Okinaga H, Matsuno A
  • Journal Title: Endocr J Volume: 60 Pages: 369-373
  • Peer Reviewed
• [Journal Article] DNA mismatch repair protein (MSH6) correlated with the responses of atypical pituitary adenomas and pituitary carcinomas to temozolomide : The national cooperative study by the Japan Society for Hypothalamic and Pituitary Tumors (2013)
  • Author(s): Hirohata T, Asano K, Ogawa Y, Takano S, Amano K, Isozaki O, Iwai Y, Sakata K, Fukuhara N, Nishioka H, Yamada S, Fujio S, Arita K, Takano K, Tominaga A, Hizuka N, Ikeda H, Osamura RY, Tahara S, Ishii Y, Kawamata T, Shimatsu A, Teramoto A, Matsuno A
  • Journal Title: J Clin Endocri Metab Volume: 98 Pages: 1130-1136
  • Peer Reviewed
• [Journal Article] A skull base osteosarcoma presenting with cerebrospinal fluid leaking in CyberKnife treatment : a case report (2013)
  • Author(s): Yamada SM, Ishii Y, Yamada S, Goto Y, Murakami M, Hoya K, Matsuno A
  • Journal Title: J Med Case Reports Volume: 7 Pages: 116-110
  • Peer Reviewed
• [Journal Article] Modified S/MAR episomal vectors for stably expressing fluorescent-protein tagged transgenes with small cell-to-cell fluctuations (2013)
  • Author(s): Mizutani A, Kikkawa E, Matsuno A, Shigenari A, Okinaga H, Murakami M, Ishida H, Tanaka M, Inoko H
  • Journal Title: Anal Biochem Volume: 443 Pages: 113-116
  • Peer Reviewed
• [Journal Article] Clinicopathological and molecular histochemical review of skull base metastasis from differentiated thyroid carcinoma (2013)
  • Author(s): Matsuno A, Murakami M, Hoya K, Yamada SM, Miyamoto S, Yamada S, Son JH, Nishido H, Ide F, Nagashima H, Sugaya M, Hirohata T, Mizutani A, Okinaga H, Ishii Y, Tahara S, Teramoto A, Osamura RY, Yamazaki K, Ishida Y
  • Journal Title: Acta Histochem Cytochem Volume: 46 Pages: 129-136
  • Peer Reviewed
• [Journal Article] Advanced therapeutic strategy for radiation-induced osteosarcoma at the skull base : a case report and review (2012)
  • Author(s): Yamada SM, Ishii Y, Kuribayashi S, Kumita S, Matsuno A
  • Journal Title: Radiat Oncol Volume: 7 Pages: 136-140
  • Peer Reviewed
• [Journal Article] Endoscopic extracapsular removal of pituitary adenoma : the importance of pretreatment of an adjacent unruptured internal carotid artery aneurysm (2012)
  • Author(s): Yamada S, Yamada SM, Hirohata T, Ishii Y, Hoya K, Murakami M, Matsuno A
  • Journal Title: Case Report Neurol Med Volume: 2012 Pages: 891847
• [Journal Article] Abnormal dynamics of growth hormone after thyrotropin-releasing hormone loading test, gonadotropin-releasing hormone loading test, and oral glucose tolerance test in mixed gonadal dysgenesis with a pituitary lesion (2011)
  • Author(s): Matsuno A, Yamada S, Yamada SM, Nakaguchi H, Hoya K, Murakami M
  • Journal Title: International Journal of Case Reports and Images (IJCRI) Volume: 2 Pages: 12-14
  • Peer Reviewed
• [Journal Article] A mechanism of acquiring temozolomide resistance during transformation of atypical prolactinoma into prolactin-producing pituitary carcinoma : case report (2011)
  • Author(s): Murakami M, Mizutani A, Asano S, Katakami H, Ozawa Y, Yamazaki K, Ishida Y, Takano K, Okinaga H, Matsuno A
  • Journal Title: Neurosurgery Volume: 68 Pages: E1761-E1767
  • Peer Reviewed
• [Journal Article] Functional molecular morphology of anterior pituitary cells, from hormone production to intracellular transport and secretion (2011)
  • Author(s): Matsuno A, Mizutani A, Okinaga H, Takano K, Yamada S, Yamada SM, Nakaguchi H, Hoya K, Murakami M, Takeuchi M, Sugaya M, Itoh J, Takekoshi S, Osamura RY
  • Journal Title: Med Mol Morphol Volume: 44 Pages: 63-70
  • Peer Reviewed
• [Journal Article] Molecular morphology of pituitary cells, from conventional immunohistochemistry to fluorescence imaging (2011)
  • Author(s): Matsuno A, Mizutani A, Okinaga H, Takano K, Yamada S, Yamada SM, Nakaguchi H, Hoya K, Murakami M, Takeuchi M, Sugaya M, Itoh J, Takekoshi S, Osamura RY
  • Journal Title: Molecules Volume: 16 Pages: 3618-3635
  • Peer Reviewed
• [Journal Article] Molecular morphological research of anterior pituitary hormone production, intracellular transport and secretion (2011)
  • Author(s): Matsuno A, Mizutani A, Okinaga H, Takano K, Yamada S, Yamada SM, Nakaguchi H, Hoya K, Murakami M, Takeuchi M, Sugaya M, Itoh J, Takekoshi S, Osamura RY
  • Journal Title: Trends in Cell and Molecular Biology Volume: 6 Pages: 1-8
  • Peer Reviewed
• [Presentation] DNA mismatch repair protein MSH6 correlated with the responses of atypical pituitary adenomas and pituitary carcinomas to temozolomide : The national cooperative study by the Japan Society for Hypothalamic and Pituitary Tumors (2013)
  • Author(s): Matsuno A
  • Organizer: The 15^<th> World Congress of Neurosurgery (WFNS)
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2013-09-10
• [Presentation] DNA mismatch repair protein MSH6 correlated with the responses of atypical pituitary adenomas and pituitary carcinomas to temozolomide : The national cooperative study by the Japan Society for Hypothalamic and Pituitary Tumors (2013)
  • Author(s): Matsuno A
  • Organizer: The 24th Annual Meeting of Asia-Pacific Endocrine Conference (APEC)
  • Place of Presentation: Dalian, China
  • Year and Date: 2013-07-14
• [Presentation] Effect of intensive resection of pseudocapsule on surgical results in no-functioning pituitary macroadenomas (2013)
  • Author(s): Ishii Y, Matsuno A, Tahara S, Teramoto A, Morita A
  • Organizer: The 24th Annual Meeting of Asia-Pacific Endocrine Conference (APEC)
  • Place of Presentation: Dalian, China
  • Year and Date: 2013-07-14
• [Presentation] DNA mismatch repair protein MSH6 correlated with the responses of atypical pituitary adenomas and pituitary carcinomas to temozolomide : The national cooperative study by the Japan Society for Hypothalamic and Pituitary Tumors (2013)
  • Author(s): Matsuno A
  • Organizer: The 6^<th> International Mt. BANDAI Symposium for Neuroscience & The 7^<th> Pan-Pacific Neurosurgery Congress (Joint Neurosurgical Convention)
  • Place of Presentation: Hawaii
  • Year and Date: 2013-02-02
• [Presentation] Functional molecular morphology of pituitary cells, from conventional immunohistochemistry to fluorescein imaging (2012)
  • Author(s): Matsuno A, Mizutani A, Murakami M, Hoya K, Nakaguchi H, Yamada SM, Hirohata T, Ishibashi S, Okinaga H
  • Organizer: The 14^<th> International Congress of Histochemistry and Cytochemistry (ICHC2012)
  • Place of Presentation: Kyoto
  • Year and Date: 2012-08-27
• [Presentation] Analyses of factors influencing the acute effect of octreotide in growth hormone-secreting adenomas (2012)
  • Author(s): Ishibashi S, Matsuno A, Mizutani A, Murakami M, Hoya K, Nakaguchi H, Yamada SM, Hirohata T, Okinaga H
  • Organizer: The 14^<th> International Congress of Histochemistry and Cytochemistry (ICHC2012)
  • Place of Presentation: Kyoto
  • Year and Date: 2012-08-27
• [Presentation] A mechanism of acquiring temozolomide resistance during transformation of atypical prolactinoma into prolactin-producing pituitary carcinoma (2012)
  • Author(s): Murakami M, Mizutani A, Hoya K, Matsuno A
  • Organizer: The 14^<th> International Congress of Histochemistry and Cytochemistry (ICHC2012)
  • Place of Presentation: Kyoto
  • Year and Date: 2012-08-27
• [Presentation] Identification of a novel interactor of human growth hormone (2012)
  • Author(s): Mizutani A, Matsuno A, Hirohata T, Tanaka M, Inoko H
  • Organizer: The 14^<th> International Congress of Histochemistry and Cytochemistry (ICHC2012)
  • Place of Presentation: Kyoto
  • Year and Date: 2012-08-27
• [Presentation] DNA mismatch repair protein MSH6 correlated with the responses of atypical pituitary adenomas and pituitary carcinomas to temozolomide : The national cooperative study by the Japan Society for Hypothalamic and Pituitary Tumors (2012)
  • Author(s): Hirohata T, Matsuno A, Osamura RY, Teramoto A
  • Organizer: The 14^<th> International Congress of Histochemistry and Cytochemistry (ICHC2012)
  • Place of Presentation: Kyoto
  • Year and Date: 2012-08-27
• [Presentation] Studies of the Japan Society for Hypothalamic and Pituitary Tumors : Temozolomide treatment of pituitary carcinoma and atypical adenoma (2012)
  • Author(s): Matsuno A
  • Organizer: The 5th Harbin International Neurosurgical Conference
  • Place of Presentation: Harbin, China
  • Year and Date: 2012-07-15
• [Presentation] A mechanism of acquiring temozolomide resistance during transformation of atypical prolactinoma into prolactin-producing pituitary carcinoma (2011)
  • Author(s): Murakami M, Mizutani A, Hoya K, Matsuno A
  • Organizer: The 10^<th> China-Japan Joint Seminar on Histochemistry and Cytochemistry (CJJSHC)
  • Place of Presentation: Beijing, China
  • Year and Date: 20111022-23
• [Presentation] Identification of novel interaction partners for human growth hormone (hGH) by the yeast two hybrid system (2011)
  • Author(s): Mizutani A, Tanaka M, Yoshimura S, Okinaga H, Takano K, Inoko H , Matsuno A
  • Organizer: The 10^<th> China-Japan Joint Seminar on Histochemistry and Cytochemistry (CJJSHC)
  • Place of Presentation: Beijing, China
  • Year and Date: 20111022-23
• [Presentation] Analyses of factors influencing the acute effect of octreotide in growth hormone-secreting adenomas (2011)
  • Author(s): Ishibashi S, Matsuno A, Mizutani A, Hoya K, Murakami M, Okinaga H
  • Organizer: The 10^<th> China-Japan Joint Seminar on Histochemistry and Cytochemistry (CJJSHC)
  • Place of Presentation: Beijing, China
  • Year and Date: 20111022-23
• [Presentation] Differential diagnosis among patients with total thyroidectomy, thyroid dysgenesis and mutations in the thyroglobulin gene by a novel ultrasensitive EIA for human thyroglobulin (2011)
  • Author(s): Katakami H, Hashida S, Iwasaki H, Hishinuma A, Fukata S, Matsuno A
  • Organizer: Ieiri T. ENDO 2011
  • Place of Presentation: Boston, USA
  • Year and Date: 20110604-07
• [Presentation] Functional molecular morphology of pituitary cells, from conventional immunohistochemistry to fluorescein imaging (2011)
  • Author(s): Matsuno A, Mizutani A, Hoya K, Murakami M, Ishibashi S, Okinaga H
  • Organizer: The 10^<th> China-Japan Joint Seminar on Histochemistry and Cytochemistry (CJJSHC)
  • Place of Presentation: Beijing, China
  • Year and Date: 2011-10-23
• [Presentation] Functional molecular morphology of pituitary cells, from conventional immunohistochemistry to fluorescein imaging (2011)
  • Author(s): Matsuno A
  • Organizer: Capital Medical University
  • Place of Presentation: Beijing, China
  • Year and Date: 2011-04-14
• [Presentation] Temozolomide treatment of malignant pituitary adenomas (2011)
  • Author(s): Matsuno A, Murakami M, Mizutani A, Nakaguchi H, Yamada SM, Hoya K, Asano S, Ozawa Y, Yamazaki K, Ishida Y, Okinaga H
  • Organizer: The 4th International Neurosurgical Winter Congress
  • Place of Presentation: Rusutsu, Hokkaido, Japan
  • Year and Date: 2011-02-09
• [Book] 4.脳腫瘍 トルコ鞍部腫瘍非機能性下垂体腺腫. 今日の神経疾患治療指針第2版 (2013)
  • Author(s): 松野彰. 水澤英洋、鈴木則宏、梶龍兒、吉良潤一、神田隆、齊藤延人 編
  • Total Pages: 360-362
  • Publisher: 医学書院
• [Book] 第5章生化学検査 A.下垂体. 標準臨床検査医学第4版 (2013)
  • Author(s): 松野彰.高木康、山田俊幸 編
  • Total Pages: 93-105
  • Publisher: 医学書院
• [Book] 今日の治療指針2013年版私はこう治療している (2013)
  • Author(s): 松野彰
  • Total Pages: 800-801
  • Publisher: 医学書院
• [Book] IV. 間脳・下垂体・傍鞍部の治療 悪性下垂体腺腫―異型性下垂体腺腫、下垂体癌. ビジュアル脳神経外科6間脳・下垂体・傍鞍部 (2013)
  • Author(s): 廣畑倫生、村上峰子、松野彰. 齋藤延人 編
  • Total Pages: 144-153
  • Publisher: メジカルビュー社
• [Book] 11章 脳腫瘍 §8 脳腫瘍各論(6) 下垂体腺腫、頭蓋咽頭腫. 脳神経外科学 改訂第11版 (2012)
  • Author(s): 松野彰. 太田富雄 総編 川原信隆、西川亮、野崎和彦、吉峰俊樹 編
  • Total Pages: 1545-1574
  • Publisher: 金芳堂
• [Book] 各論編 第2章 基礎知識D. 下垂体前葉疾患各論35. 下垂体癌と異型性下垂体腺腫. 下垂体疾患診療マニュアル診断と治療 (2012)
  • Author(s): 松野彰、村上峰子、水谷晃子. 平田結喜緒、山田正三、成瀬光栄 編
  • Total Pages: 216-218
• [Book] 下垂体腺腫の原因遺伝子と視床下部・下垂体のクロストーク. 日本臨床分子形態学会編 病気の分子形態学 (2011)
  • Author(s): 松野彰
  • Total Pages: 342-344
  • Publisher: 学際企画