Brain mechanism mediating estrogen feedback controlling follicular development and ovulation

2013 Fiscal Year Final Research Report

• Project/Area Number: 23380163
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied animal science
• Research Institution: Nagoya University
• Principal Investigator: TSUKAMURA Hiroko 名古屋大学, 生命農学研究科, 教授 (00212051)
• Co-Investigator(Renkei-kenkyūsha): ISHII Hirotaka 日本医科大学, 医学部, 助手 (20445810) ; HIRABAYASHI Masumi 生理学研究所, 行動・代謝分子解析センター, 准教授 (20353435)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: キスペプチン / Kiss1 / メタスチン / GPR54 / エストロジェン / ヒストン / エピジェネティック / 性腺刺激ホルモン

Research Abstract

The present study aimed to investigate the brain mechanism mediating estrogen feedback to regulate two modes (pulse and surge) of gonadotropin-releasing hormone (GnRH)/gonadotropin release. Kisspeptin neurons located in the anteroventral periventricular nucleus (AVPV) and hypothalamic arcuate nucleus (ARC) are considered to control follicular development and ovulation via GnRH pulse and surge, respectively. In vivo and in vitro study using rats and mice revealed that epigenetic mechanism is involved in the both negative and positive feedback effects of estrogen to control expression of kisspeptin located in the AVPV and ARC. Since kisspeptin neurons are considered to govern reproductive function in mammals, the present results are expected to be applied to increase animal production efficiency in the future.

Research Products

• [Journal Article] KISS1 Gene Expression in the Developing Brain of Female Pigs at Preand PostPeri-pubertal Periods (2014)
  • Author(s): Ieda, N., Uenoyama, Y., Tajima, Y., Nakata, T., Kano, M., Naniwa, Y., Watanabe, Y., Minabe, S., Tomikawa, J., Inoue, N., Matsuda, F., Ohkura, S., Maeda, K.-I. and Tsukamura, H
  • Journal Title: J Reprod Dev Volume: (In press)
  • Peer Reviewed
• [Journal Article] Effects of full-length kisspeptin administration on follicular development in Japanese Black beef cows (2013)
  • Author(s): Naniwa, Y., Nakatsukasa, K., Setsuda, S., Oishi, S., Fujii, N., Matsuda, F., Uenoyama, Y., Tsukamura, H., Maeda, K.-I. and Ohkura, S
  • Journal Title: J Reprod Dev Volume: 59(6) Pages: 588-94
  • Peer Reviewed
• [Journal Article] Molecular cloning and identification of transcriptional regulatory domain of the goat neurokinin B gene TAC3 (2013)
  • Author(s): Suetomi, Y., Matsuda, F., Uenoyama, Y., Maeda, K.-I., Tsukamura, H. and Ohkura, S
  • Journal Title: J Reprod Dev Volume: 59(5) Pages: 463-469
  • Peer Reviewed
• [Journal Article] Kisspeptin and GnRH pulse generation (2013)
  • Author(s): Okamura, H., Tsukamura, H., Ohkura, S., Uenoyama, Y., Wakabayashi, Y. and Maeda, K.-I
  • Journal Title: Adv Exp Med Biol Volume: 784 Pages: 297-323
  • DOI: 10.1007/978-1-4614-6199-9_14
  • Peer Reviewed
• [Journal Article] Chronic peripheral administration of kappa-opioid receptor antagonist advances puberty onset associated with acceleration of pulsatile luteinizing hormone secretion in female rats (2013)
  • Author(s): Nakahara T, Uenoyama Y, Iwase A, Oishi S, Nakamura S, Minabe S, Watanabe Y, Deura C, Noguchi T, Fujii N, Kikkawa F, Maeda K, Tsukamura H
  • Journal Title: J. Reprod. Dev Volume: 59 Pages: 479-84
  • Peer Reviewed
• [Journal Article] Microarray analysis of perinatal-estrogen-induced changes in gene expression related to brain sexual differentiation in mice (2013)
  • Author(s): Sakakibara, M., Uenoyama, Y., Minabe, S., Watanabe, Y., Deura, C., Nakamura, S., Suzuki, G., Maeda, K.-I., and Tsukamura, H
  • Journal Title: PLOS ONE Volume: 8(11) Pages: e79437
  • DOI: 10.1371/journal.pone.0079437
  • Peer Reviewed
• [Journal Article] Dynorphin-kappa opioid receptor signaling partly mediates estrogen negative feedback effect on LH pulses in female rats (2013)
  • Author(s): Mostari, M.P., Ieda, N., Deura, C., Minabe, S., Yamada, S., Uenoyama, Y., Maeda, K.-I. and Tsukamura, H
  • Journal Title: J Reprod Dev Volume: 59(3) Pages: 266-72
  • Peer Reviewed
• [Journal Article] Different critical perinatal periods and hypothalamic sites of oestradiol action in the defeminization of LH surge and lordosis capacity in the rat (2013)
  • Author(s): Sakakibara, M., Deura, C., Minabe, S., Iwata, Y., Uenoyama, Y., Maeda, K.-I. and Tsukamura, H
  • Journal Title: J Neuroendocrinol Volume: 25 Pages: 251-259
  • DOI: 10.1111/j.1365-2826.2012.02389.x
  • Peer Reviewed
• [Journal Article] Oestrogen-dependent suppression of pulsatile luteinizing hormone secretion and Kiss1 mRNA expression in the arcuate nucleus during late lactation in rats (2012)
  • Author(s): Yamada, S., Uenoyama, Y., Deura, C., Minabe, S., Naniwa, Y., Iwata, K., Kawata, M., Maeda, K.-I., Tsukamura, H
  • Journal Title: J Neuroendocrinol Volume: 24 Pages: 1234-1242
  • DOI: 10.1111/j.1365-2826.2012.02330.x
  • Peer Reviewed
• [Journal Article] Epigenetic regulation of Kiss1 gene expression mediating estrogen-positive feedback action in themouse brain (2012)
  • Author(s): Tomikawa, J., Uenoyama, Y., Ozawa M., Fukanuma, T., Takase, K., Goto, T., Abe, H., Ieda, N., Minabe, S., Deura, C., Inoue, N., Sanbo, M., Tomita, K., Hirabayashi, M., Tanaka, S., Imamura, T., Okamura, H., Maeda, K.-I., Tsukamura, H
  • Journal Title: Proceedings of National Academy of Sciences of the United States of America Pages: E1294-E1301
  • DOI: 10.1073/pnas.1114245109
  • Peer Reviewed
• [Journal Article] Kisspeptin neurons mediate reflex ovulation in the musk shrew (Suncus murinus) (2011)
  • Author(s): Inoue, N., Sasagawa, K., Ikai, K., Sasaki, Y., Tomikawa, J., Oishi, S., Fujii, N., Uenoyama, Y., Ohmori, Y., Yamamoto, N., Hondo, E., Maeda, K.-I. and Tsukamura, H
  • Journal Title: Proc Natl Acad Sci USA Volume: 108 Pages: 17527-17532
  • Peer Reviewed
• [Journal Article] Morphological evidence for direct interaction between kisspeptin and GnRH neurones at the median eminence of the male goat : an immunoelectron microscopic study (2011)
  • Author(s): Matsuyama, S., Ohkura, S., Mogi, K., Wakabayashi, Y., Mori, Y., Tsukamura, H., Maeda, K.-I., Ichikawa, M. and Okamura, H
  • Journal Title: Neuroendocrinology Volume: 94 Pages: 323-332
  • Peer Reviewed
• [Journal Article] Single-stranded noncoding RNAs mediate local epigenetic alterations at gene promoters in rat cell lines (2011)
  • Author(s): Tomikawa, J., Shimokawa, H., Uesaka, M., Yamamoto, N., Mori, Y., Tsukamura, H., Maeda, K.-I., and Imamura, T
  • Journal Title: The Journal of Biological Chemistry Volume: 286 Pages: 34788-34788
  • Peer Reviewed
• [Journal Article] Ultrastructural evidence of kisspeptin-gonadotrophin-releasing hormone interaction in the median eminence of female rats : implication of axo-axonal regulation of GnRH release (2011)
  • Author(s): Uenoyama, Y., Inoue, N., Pheng, V., Homma, T., Takase, K., Yamada, S., Ajiki, K., Ichikawa, M., Okamura, H., Maeda, K.-I., and Tsukamura, H
  • Journal Title: Journal of Neuroendocrinology Volume: 23 Pages: 863-870
  • Peer Reviewed
• [Journal Article] Analysis of pulsatile and surge-like luteinizing hormone secretion with frequent blood sampling in female mice (2011)
  • Author(s): Minabe, S., Uenoyama, Y., Tsukamura, H. and Maeda, K.-I
  • Journal Title: Journal of Reproduction and Development Volume: 57 Pages: 660-664
  • Peer Reviewed
• [Journal Article] Involvement of neurokinin receptors in the control of pulsatile luteinizing hormone secretion in rats (2011)
  • Author(s): Noritake, K., Matsuoka, T., Ohsawa, T., Shimomura, K., Sanbuissho, A., Uenoyama, Y., Maeda, K.-I., and Tsukamura, H
  • Journal Title: Journal of Reproduction and Development Volume: 57 Pages: 409-415
  • Peer Reviewed
• [Journal Article] Testicular toxicity induced by a triple neurokinin receptor antagonist in male dogs (2011)
  • Author(s): Noritake, K.-I., Suzuki, J., Matsuoka, T., Makino, T., Ohnishi, H., Shimomura, K., Uenoyama, Y., Tsukamura, H., Maeda, K.-I. and Sanbuissho, A
  • Journal Title: Reproductive Toxicology Volume: 31 Pages: 440-446
  • Peer Reviewed
• [Journal Article] Activation of Neuropeptide FF Receptors by Kisspeptin Receptor Ligands (2011)
  • Author(s): Oishi, S., Misu, R., Tomita, K., Setsuda, S., Masuda, R., Ohno, H., Naniwa, Y., Ieda, N., Inoue, N., Ohkura, S., Uenoyama, Y., Tsukamura, H., Maeda, K.-I., Hirasawa, A., Tsujimoto, G. and Fujii N
  • Journal Title: ACS Medicinal Chemistry Letters Volume: 2 Pages: 53-57
  • Peer Reviewed
• [Presentation] 哺乳類の脳における性ステロイドのorganizational およびfunctional 効果 : 生殖中枢キスペプチンニューロンの性分化とキスペプチン発現のエピジェネティック制御機構 (2013)
  • Author(s): 束村博子
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド神戸国際会議場(兵庫県神戸市)
  • Year and Date: 20131203-06
• [Presentation] ほ乳類の脳の性分化と卵胞発育・排卵中枢の制御を担う性ステロイドのはたらき (2013)
  • Author(s): 束村博子
  • Organizer: 第40回日本神経内分泌学会学術集会/第38回日本比較内分泌学会大会 日本比較内分泌学会企画委員会主催シンポジウム
  • Place of Presentation: 宮崎市民プラザ(宮崎県宮崎市)
  • Year and Date: 20131024-26
• [Presentation] 種を超えて生殖を制御する神経ペプチド : キスペプチン (2013)
  • Author(s): 束村博子
  • Organizer: 第27回日本下垂体研究会学術集会
  • Place of Presentation: 天童ホテル(山形県天童市)
  • Year and Date: 20130809-11
• [Presentation] Lactational anestrus and Kisspeptin signaling (2013)
  • Author(s): Tsukamura, H
  • Organizer: 5th Parental Brain conference
  • Place of Presentation: Regensburg (Germany)
  • Year and Date: 20130711-14
• [Presentation] Kisspeptin control of gonadotropin release. Recent advances in the central control of reproduction (2013)
  • Author(s): Tsukamura, H. (University of Nagoya, Nagoya, Japon)
  • Organizer: INRA(the French National Institute for Agricultural Research)
  • Place of Presentation: Centre INRA, Conference hall(France)
  • Year and Date: 20130410-12
• [Presentation] 生殖中枢キスペプチンニューロンに対するエストロゲンのエピジェネティック制御 (2013)
  • Author(s): 束村博子, 冨川順子, 上野山賀久, 前多敬一郎
  • Organizer: 第90回日本生理学会大会
  • Place of Presentation: タワーホール船堀(東京)
  • Year and Date: 20130327-29
• [Presentation] キスペプチンニューロンによる卵胞発育と排卵制御の神経内分泌メカニズム (2013)
  • Author(s): 束村博子
  • Organizer: Nordiscience forum 2013
  • Place of Presentation: ウエスティン都ホテル京都西館4階『瑞穂(みずほ)の間』(京都市)
  • Year and Date: 2013-06-08
• [Presentation] Epigenetic regulation of kiss1 gene expression mediating estrogen positive feedback action (2012)
  • Author(s): Tsukamura, H., Tomikawa, J., Uenoyama, Y. and Maeda, K.-I
  • Organizer: 2nd World Conference on Kisspeptin Signaling in the Brain
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 20121106-09
• [Presentation] エストロジェンの正のフィードバックを仲介するKiss1発現調節のエピジェネティクメカニズム (2012)
  • Author(s): 束村博子, 冨川順子, 上野山賀久, 前多敬一郎
  • Organizer: 第39回日本神経内分泌学会学術集会
  • Place of Presentation: 北九州国際会議場(福岡県北九州市)
  • Year and Date: 20120928-29
• [Presentation] 視床下部弓状核特異的なキスペプチン発現を制御する分子機構 (2012)
  • Author(s): 束村博子, 前多敬一郎, 上野山賀久
  • Organizer: 第105回日本繁殖生物学会大会
  • Place of Presentation: 筑波大学大学会館(茨城県つくば市)
  • Year and Date: 20120905-08
• [Presentation] エストレジェンフィードバックによるキスペプチン遺伝子発現を制御の分子機構 (2012)
  • Author(s): 束村 博子, 上野山 賀久, 冨川 順子, 井上 直子, 大蔵 聡, 前多 敬一郎
  • Organizer: 第9回GPCR研究会
  • Place of Presentation: 日本未来科学館 みらいCAN ホール(東京)
  • Year and Date: 20120511-12
• [Presentation] キスペプチンニューロンによるGnRH パルス/サージ発生制御機構 (2012)
  • Author(s): 束村 博子, 上野山 賀久, 冨川 順子, 大蔵 聡, 井上 直子, 前多 敬一郎
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 20120419-21
• [Presentation] 種を超えて生殖を制御する神経ペプチド : キスペプチン (2012)
  • Author(s): 束村博子
  • Organizer: 日本下垂体研究会第27回学術集会
  • Place of Presentation: 天童ホテル(山形県天童市)
  • Year and Date: 2012-08-11
• [Presentation] キスペプチンー生殖を支配する神経ペプチドー (2012)
  • Author(s): 束村博子
  • Organizer: 第12回日本内分泌学会中国支部学術集会
  • Place of Presentation: 松江テルサ(島根・松江)
  • Year and Date: 2012-03-03
• [Presentation] Long-term neonatal estrogen exposure suppresses pulsatile LH release by an irreversible suppression of arcuate kiss1 gene expressions through ER alfa in rodents (2011)
  • Author(s): Tsukamura H., Homma T., Ieda N., Minabe S., Inamoto Y., Yoshida K., Tomikawa J., Yamada S., Ohkura S., Inoue N., Uenoyama Y., Maeda K.-I
  • Organizer: The Second World Congress on Reproductive Biology
  • Place of Presentation: Cairns, Australia
  • Year and Date: 20111009-12
• [Presentation] GnRH pulse generation and it's application to the manipulation of follicular development and ovulation (2011)
  • Author(s): Tsukamura H
  • Organizer: The Joint Symposium of Thai and Japanese Societies for Animal Reproduction
  • Place of Presentation: チュラロンコン大学獣医学部(タイ国・バンコク)
  • Year and Date: 20110929-30
• [Presentation] 脳の性分化 : 発達脳へのステロイド感作とキスペプチンニューロン (2011)
  • Author(s): 束村博子
  • Organizer: 国立医薬品食品衛生研究所特別講演会
  • Place of Presentation: 東京
  • Year and Date: 2011-11-30