Evolution of calcium homeostasis: the functional study of calcitonin in cyclostome and cartilaginous fish

• Project/Area Number: 18K06312
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44040:Morphology and anatomical structure-related
• Research Institution: Kanazawa University
• Principal Investigator: Toshio Sekiguchi 金沢大学, 環日本海域環境研究センター, 准教授 (40378568)
• Co-Investigator(Kenkyū-buntansha): 坂本 竜哉 岡山大学, 自然科学研究科, 教授 (10294480) ; 鈴木 信雄 金沢大学, 環日本海域環境研究センター, 教授 (60242476)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: カルシトニン / ヌタウナギ / アカエイ / 円口類 / 軟骨魚類 / 血中カルシウム濃度調節 / 血中カルシウム調節 / 比較内分泌学 / 生理機能の進化 / 進化

Outline of Final Research Achievements

To elucidate the evolution of the regulation mechanism of serum calcium level involved in calcitonin (CT), functional analysis of CT in cyclostome and cartilaginous fish were performed.
In hagfish, the CT and its receptor candidate gene were identified. Hagfish CT stimulated mammalian cells expressed by a CT receptor candidate. In addition, oral administration of calcium increased the serum calcium level, whereas hagfish CT concentration did not change. In red stingray, the CT gene was cloned from the ultimobranchial gland. Measurement of serum CT level using ELISA and serum calcium level revealed no correlation between serum CT level and serum calcium concentration. Contrary, serum CT level showed a positive correlation with gonadal weight, suggesting that CT is associated with reproductive function in cartilaginous fish.

Academic Significance and Societal Importance of the Research Achievements

脊椎動物では血中のカルシウム濃度が一定になるようにホルモンで調節されているが、この調節機構の起源や進化は不明である。本研究では、血中カルシウム濃度低下に関わる代表的なホルモンであるカルシトニン(CT)に焦点を当て、原始的な脊椎動物の円口類と軟骨魚類での役割を解析した結果、硬骨魚類よりも原始的な脊椎動物では、CTが血中カルシウム濃度調節以外の役割を持つことが明らかになった。特に軟骨魚類では、生殖機能との関わりが示された。今後、これらの動物におけるCT機能の解明とともに真の血中カルシウム調節ホルモンの同定が期待される。

Research Products

• [Journal Article] Profiles of 5-reduced androgens in human and eel: 5 -dihydrotestosterone 1 and 11-ketodihydrotestosterone are active androgens produced in eel gonads. (2021)
  • Author(s): Yazawa, T., Inaba, H., Imamichi, Y., Sekiguchi, T., Uwada, J., Islam, M.S., Orisaka, M., Mikami, D., Ida, T., Sato, T., Miyashiro, Y., Takahashi, S., Khan, R. I., Suzuki, N., Umezawa, A. and Kitano, T.
  • Journal Title: Frontiers in Endocrinology Volume: -
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 11-ketotestosterone is a major androgen produced in porcine 1 adrenal and testis. (2021)
  • Author(s): Yazawa, T., Sato, T., Nemoto, T., Nagata, S., Imamichi, Y., Kitano, T., Sekiguchi, T., Uwada, J., Islam, M.S., Tanguchi, T., Mikami, D., Nakajima, I., Takahashi, S., Khan, R.I., Suzuki, N., Umezawa, A. and Ida, T.
  • Journal Title: The Journal of Steroid Biochemistry and Molecular Biology, Volume: -
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] De novo transcriptome analysis and gene expression profiling in fish scales isolated from Carassius auratus during space flight: A impact of melatonin on the expression of genes responsive to space radiation. (2020)
  • Author(s): Furusawa, Y., Yamamoto, T., Hattori, A., Suzuki, N., Sekiguchi, T., Hirayama, J. and Tabuchi, Y.
  • Journal Title: Molecular Medicine Reports Volume: 22 Pages: 2627-2636
  • Peer Reviewed
• [Journal Article] Oral administration of melatonin contained in drinking water increased bone strength in naturally aged mice. (2020)
  • Author(s): Igarashi-Migitaka, J., Seki, A., Ikegame, M., Honda, M., Sekiguchi, T., Mishima, H., Shimizu, N., Matsubara, H., Srivastav, A.K., Hirayama, J., Maruyama, Y., Kamijo-Ikemori, A., Hirata, K., Hattori, A. and Suzuki, N.
  • Journal Title: Acta Histochemica Volume: 122 Pages: 151596-151596
  • Peer Reviewed
• [Journal Article] Detection of RANKL-producing cells and osteoclastic activation by the addition of exogenous RANKL in the regenerating scales of goldfish. (2020)
  • Author(s): Yamamoto, T., Ikegame, M., Kawago, U., Tabuchi, Y., Hirayama, J., Sekiguchi, T., Furusawa, Y., Yachiguchi, K., Matsubara, H., Urata, M., Hattori, A. and Suzuki, N.
  • Journal Title: Biological Science in Space Volume: 34 Pages: 400-403
  • NAID: 130007884615
  • Peer Reviewed
• [Journal Article] Expression of sclerostin in the regenerating scales of goldfish and its increase under microgravity during space flight. (2020)
  • Author(s): Yamamoto, T., Ikegame, M., Hirayama, J., Kitamura, K., Tabuchi, Y., Furusawa, Y., Sekiguchi, T., Endo, M., Mishima, H., Seki, A., Yano, S., Matsubara, H., Hattori, A. and Suzuki, N.
  • Journal Title: Biomedical Research (Tokyo) Volume: 41 Pages: 279-288
  • NAID: 130007948844
  • Peer Reviewed
• [Journal Article] Evaluation of 17beta-hydroxysteroid dehydrogenase activity using androgen receptor-mediated transactivation. (2020)
  • Author(s): Yazawa, T., Imamichi, Y., Uwada, J., Sekiguchi, T., Mikami, D., Kitano, T., Ida, T. Sato, T., Nemoto, T., Nagata, S., Khan, R., Takahashi, S., Ushikubi, F., Taniguchi, A., Suzuki, N. and Umezawa, A.
  • Journal Title: The Journal of Steroid Biochemistry and Molecular Biology Volume: 196 Pages: 105493-105493
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Evaluation of 17β-hydroxysteroid dehydrogenase activity using androgen receptor-mediated transactivation (2020)
  • Author(s): Yazawa Takashi、Imamichi Yoshitaka、Uwada Junsuke、Sekiguchi Toshio、Mikami Daisuke、Kitano Takeshi、Ida Takanori、Sato Takahiro、Nemoto Takahiro、Nagata Sayaka、Islam Khan Md. Rafiqul、Takahashi Satoru、Ushikubi Fumitaka、Suzuki Nobuo、Umezawa Akihiro、Taniguchi Takanobu
  • Journal Title: The Journal of Steroid Biochemistry and Molecular Biology Volume: 196 Pages: 105493-105493
  • DOI: 10.1016/j.jsbmb.2019.105493
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Influence of Benz[a]anthracene on Bone Metabolism and on Liver Metabolism in Nibbler Fish, Girella punctata (2020)
  • Author(s): Zanaty Mohamed I.、Sawada Niina、Kitani Yoichiro、Nassar Hossam F.、Mahmoud Hamada M.、Hayakawa Kazuichi、Sekiguchi Toshio、Ogiso Shouzo、Tabuchi Yoshiaki、Urata Makoto、Matsubara Hajime、Takeuchi Yutaka、Hattori Atsuhiko、Srivastav Ajai K.、Amornsakun Thumronk、Suzuki Nobuo
  • Journal Title: International Journal of Environmental Research and Public Health Volume: 17 Issue: 4 Pages: 1391-1391
  • DOI: 10.3390/ijerph17041391
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effect of Polycyclic Aromatic Hydrocarbons on Development of the Ascidian Ciona intestinalis Type A (2020)
  • Author(s): Sekiguchi Toshio、Akitaya Hiroshi、Nakayama Satoshi、Yazawa Takashi、Ogasawara Michio、Suzuki Nobuo、Hayakawa Kazuichi、Wada Shuichi
  • Journal Title: International Journal of Environmental Research and Public Health Volume: 17 Issue: 4 Pages: 1340-1340
  • DOI: 10.3390/ijerph17041340
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cyclooxygenase‐2 is acutely induced by CCAAT/enhancer‐binding protein β to produce prostaglandin E 2 and F 2α following gonadotropin stimulation in Leydig cells (2019)
  • Author(s): Yazawa Takashi、Imamichi Yoshitaka、Yuhki Koh‐ichi、Uwada Junsuke、Mikami Daisuke、Shimada Masayuki、Miyamoto Kaoru、Kitano Takeshi、Takahashi Satoru、Sekiguchi Toshio、Suzuki Nobuo、Rafiqul Islam Khan Md.、Ushikubi Fumitaka、Umezawa Akihiro、Taniguchi Takanobu
  • Journal Title: Molecular Reproduction and Development Volume: 86 Issue: 7 Pages: 786-797
  • DOI: 10.1002/mrd.23163
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Development of a system for measuring calcitonin in the stingray Dasyatis akajei (a cartilaginous fish): the possible involvement of stingray calcitonin in gonadal development (2019)
  • Author(s): Takagi Takashi、Sekiguchi Toshio、Sasayama Yuichi、Hattori Atsuhiko、Watanabe Takushi X.、Kitani Yoichiro、Tabuchi Yoshiaki、Matsubara Hajime、Srivastav Ajai K.、Hai Tran Ngoc、Amornsakun Thumronk、Suzuki Nobuo
  • Journal Title: International Aquatic Research Volume: 11 Issue: 3 Pages: 267-276
  • DOI: 10.1007/s40071-019-00236-0
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Gadolinium at Low Concentration Suppresses both Osteoclastic and Osteoblastic Activities in the Scales of Goldfish (2019)
  • Author(s): Suzuki Nobuo、Watanabe Kazuki、Sekimoto Aika、Urata Makoto、Zanaty Mohamed Ibrahim、Sekiguchi Toshio、Kitani Yoichiro、Matsubara Hajime、Srivastav Ajai Kumar、Hattori Atsuhiko
  • Journal Title: American Journal of Environmental Sciences Volume: 15 Issue: 4 Pages: 137-144
  • DOI: 10.3844/ajessp.2019.137.144
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Physiological Role of a Calcitonin-Like Substance in the Life Cycle of the Lamprey, Lampetra japonica (Cyclostomata) (2019)
  • Author(s): Nobuo Suzuki、Toshio Sekiguchi、Koji Yachiguchi、Makoto Urata、Yasuko Kinoshita、Hajime Matsubara、Kiyoshi Asahina、Akira Kambegawa、Ajai Kumar Srivastav
  • Journal Title: International Journal of Zoological Investigations Volume: 05 Issue: 02 Pages: 23-30
  • DOI: 10.33745/ijzi.2019.v05i02.003
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Melatonin is a potential drug for the prevention of bone loss during space flight (2019)
  • Author(s): Ikegame Mika、7名、Sekiguchi Toshio、43名、Suzuki Nobuo
  • Journal Title: Journal of Pineal Research Volume: 67 Issue: 3 Pages: 1-13
  • DOI: 10.1111/jpi.12594
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Transcriptional Regulation of Ovarian Steroidogenic Genes; Recent Findings Obtained from Stem Cell-derived Steroidogenic Cells. (2019)
  • Author(s): Yazawa, T., Imamichi, Y., Sekiguchi, T., Miyamoto, K., Uwada, J., Khan, R., Suzuki, N., Umezawa A. and Taniguchi, T.
  • Journal Title: BioMed Research International Volume: 8973076 Pages: 1-13
  • DOI: 10.1155/2019/8973076
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Molecular characterizat ion of putative calcitonin gene-related peptide receptors and expression of calcitonin gene-related peptide and its receptor in the early development of flounder, Paralichthys olivaceus. (2018)
  • Author(s): Sekiguchi, T., Suzuki, T., Kurokawa, T., Amornsakun, T., Hai, T.N., Srivastav, A.K. and Suzuki, N.
  • Journal Title: International Journal of Zoological Investigations Volume: 4 Pages: 106-117
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Molecular mechanism of the suppression of larval skeleton by polycyclic aromatic hydrocarbons in early development of sea urchin Hemicentrotus pulcherrimus. (2018)
  • Author(s): Sekiguchi, T., Yachiguchi, K., Kiyomoto, M., Ogiso, S., Wada, S., Tabuchi, Y., Hong, C.-S., Srivastav, A.K., Archer, S., Pointing, S.B., Hayakawa, K. and Suzuki, N.
  • Journal Title: Fisheries Science Volume: 84 Issue: 6 Pages: 1073-1079
  • DOI: 10.1007/s12562-018-1245-y
  • NAID: 40021690251
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The Calcitonin/Calcitonin Gene-Related Peptide Family in Invertebrate Deuterostomes (2018)
  • Author(s): Sekiguchi, T.
  • Journal Title: Frontiers in Endocrinology Volume: 9 Pages: 695-695
  • DOI: 10.3389/fendo.2018.00695
  • Peer Reviewed / Open Access
• [Book] Amphioxus calcitonin family peptide. In “Handbook of Hormones: Comparative Endocrinology for Basic and Clinical Research”. H. Ando, K. Ukena, and S. Nagata. 2nd eds. (2021)
  • Author(s): Sekiguchi, T.
  • Publisher: ELSEVIER, Oxford, United Kingdom
• [Book] Echinoderm calcitonin-type peptide. In “Handbook of Hormones: Comparative Endocrinology for Basic and Clinical Research”. H. Ando, K. Ukena, and S. Nagata. 2nd eds. (2021)
  • Author(s): Sekiguchi, T.
  • Publisher: ELSEVIER, Oxford, United Kingdom
• [Book] Gastrin family. In “Handbook of Hormones: Comparative Endocrinology for Basic and Clinical Research”. H. Ando, K. Ukena, and S. Nagata. 2nd eds. (2021)
  • Author(s): Sekiguchi, T.
  • Publisher: ELSEVIER, Oxford, United Kingdom
• [Book] Gastrin. In “Handbook of Hormones: Comparative Endocrinology for Basic and Clinical Research”. H. Ando, K. Ukena, and S. Nagata. 2nd eds. (2021)
  • Author(s): Sekiguchi, T.
  • Publisher: ELSEVIER, Oxford, United Kingdom
• [Book] Cholecystokinin. In “Handbook of Hormones: Comparative Endocrinology for Basic and Clinical Research”. H. Ando, K. Ukena, and S. Nagata. 2nd eds. (2021)
  • Author(s): Sekiguchi, T.
  • Publisher: ELSEVIER, Oxford, United Kingdom
• [Book] Caerulein. In “Handbook of Hormones: Comparative Endocrinology for Basic and Clinical Research”. H. Ando, K. Ukena, and S. Nagata. 2nd eds. (2021)
  • Author(s): Sekiguchi, T.
  • Publisher: ELSEVIER, Oxford, United Kingdom
• [Book] 消化管関連ペプチドが拓く恒常性フロンティア. 「臓器連環による生体恒常性の破綻と疾患」 春日 雅人編集 (2019)
  • Author(s): 4.佐藤貴弘，井田隆徳，関口俊男，中町智哉，児島将康
  • Publisher: 羊土社
  • ISBN: 9784758103787