Elucidation of the function of neuroestrogen on feeding behavior.

• Project/Area Number: 17K16172
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Endocrinology
• Research Institution: Fujita Health University
• Principal Investigator: Hayashi Takanori 藤田医科大学, 医学部, 講師 (40724315)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: エストロゲン / 食欲 / ニューロエストロゲン / アロマターゼ / ニューロステロイド / MC4R / 女性医学 / 摂食

Outline of Final Research Achievements

In the nerve cells of the brain, estrogen is locally and independently produced, and is involved in various physiological functions. The estrogen synthesized in nerve cells is called neuroestrogen. It is distinguished from estrogen supplied from the ovary and other tissues, and is studied independently.
Although the appetite-suppressing effect of estrogen is clear, the relationship between neuroestrogen and appetite is unknown. So, a detailed analysis was performed using the mouse hypothalamic nerve cell line N38. As a result, it was revealed that in the hypothalamus, neuroestrogens independently act on the appetite regulating nerves to suppress appetite.

Academic Significance and Societal Importance of the Research Achievements

本研究により，独自に調節されているニューロエストロゲンが直接視床下部神経で作用していることが明らかになった。今回のようにエストロゲンとニューロエストロゲンを区別して研究して解析することで，ニューロエストロゲンの神経伝達物質様作用を明らかにすることで，これまで治療困難であった過食，拒食，イライラ食いなどの予防・治療開発につなげたいと考えている。

Research Products

• [Journal Article] Lack of association of ovariectomy-induced obesity with overeating and the reduction of physical activities. (2019)
  • Author(s): Nishio E, Hayashi T, Nakatani M, Aida N, Suda R, Fujii T, Wakatsuki T, Honda S, Harada N, Shimono Y.
  • Journal Title: Biochemistry and Biophysics Reports Volume: 20 Pages: 100671-100671
  • DOI: 10.1016/j.bbrep.2019.100671
  • Peer Reviewed / Open Access
• [Journal Article] miR-221 Targets QKI to Enhance the Tumorigenic Capacity of Human Colorectal Cancer Stem Cells. (2019)
  • Author(s): Mukohyama J, Isobe T, Hu Q, Hayashi T, Watanabe T, Maeda M, Yanagi H, Qian X, Yamashita K, Minami H, Mimori K, Sahoo D, Kakeji Y, Suzuki A, Dalerba P, Shimono Y.
  • Journal Title: Cancer Research Volume: 79 Issue: 20 Pages: 5151-5158
  • DOI: 10.1158/0008-5472.can-18-3544
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A Hypoglycemia-inducing Giant Borderline Phyllodes Tumor Secreting High-molecular-weight Insulin-Like Growth Factor II: Immunohistochemistry and a Western Blot Analysis (2018)
  • Author(s): Masahiro Hikichi, Yuka Kiriyama, Takanori Hayashi, Kaori Ushimado, Naomi Kobayashi, Makoto Urano, Makoto Kuroda, Toshiaki Utsumi
  • Journal Title: Internal Medicine Volume: 57 Issue: 2 Pages: 237-241
  • DOI: 10.2169/internalmedicine.9287-17
  • NAID: 130006309182
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed
• [Journal Article] Forskolin increases the effect of everolimus on aromatase inhibitor-resistant breast cancer cells (2018)
  • Author(s): Hayashi Takanori、Hikichi Masahiro、Yukitake Jun、Wakatsuki Toru、Nishio Eiji、Utsumi Toshiaki、Harada Nobuhiro
  • Journal Title: Oncotarget Volume: 9 Issue: 34 Pages: 23451-23461
  • DOI: 10.18632/oncotarget.25217
  • Peer Reviewed / Open Access
• [Journal Article] Estradiol suppresses phosphorylation of ERα serine 167 through upregulation of PP2A in breast cancer cells (2017)
  • Author(s): Hayashi Takanori、Hikichi Masahiro、Yukitake Jun、Harada Nobuhiro、Utsumi Toshiaki
  • Journal Title: Oncology Letters Volume: 14 Pages: 8060-8065
  • DOI: 10.3892/ol.2017.7216
  • Peer Reviewed
• [Presentation] ニューロエストロゲンが摂食行動に及ぼす影響 (2019)
  • Author(s): 林孝典，西尾永司，本田伸一郎，原田信広
  • Organizer: 女性医学会
• [Presentation] ニューロエストロゲンが摂食行動に及ぼす影響とメカニズム (2018)
  • Author(s): 林孝典，本田伸一郎，原田信広
  • Organizer: ステロイドホルモン学会
• [Presentation] ニューロエストロゲンが食欲に及ぼす影響 (2018)
  • Author(s): 林孝典，本田伸一郎，原田信広
  • Organizer: 91回 日本生化学会大会
  • Invited
• [Presentation] 摂食関連因子にニューロエストロゲンが及ぼす影響 (2017)
  • Author(s): 林孝典
  • Organizer: 日本生化学会