Study of the function and formation of sexually dimorphic nucleus

• Project/Area Number: 17K08567
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: Saitama University
• Principal Investigator: Tsukahara Shinji 埼玉大学, 理工学研究科, 教授 (90318824)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 性的二型核 / 性ホルモン / 性分化 / 性差 / 思春期 / カルビンディン

Outline of Final Research Achievements

Nucleus exhibiting morphological sex differences are called sexual dimorphic nucleus. Physiological functions and formation mechanisms of sexually dimorphic nuclei are being studied for a long time; however, they have not yet been understood completely. The current study using rodent models showed that the sexually dimorphic nucleus of the preoptic area is involved in the control of sexual behavior. It was also found that testicular androgens and ovarian estrogens during the puberty play an important role in the formation of sexually dimorphic nuclei.

Academic Significance and Societal Importance of the Research Achievements

性的二型核は、実験動物だけでなくヒトの脳にも存在する。本研究の成果は、単に実験動物の脳の性差を明らかにするのでなく、ヒトの脳の性差の理解に資するものである。本研究の成果を社会に発信することで、こころの性に関する理解が深まり、性的マイノリティに対する差別と偏見が無くなることが期待される。また、幾つかの神経疾患の罹患率には性差がある。このことは、疾患の発症メカニズムに性差があることを示唆しており、本研究の成果が疾患発症機構の解明に役立つ。

Research Products

• [Journal Article] Estrogenic action by tris(2,6-dimethylphenyl) phosphate impairs the development of female reproductive functions (2020)
  • Author(s): Sano Kazuhiro、Matsukami Hidenori、Suzuki Go、Htike Nang Thinn Thinn、Morishita Masahiro、Win-Shwe Tin-Tin、Hashimoto Shunji、Kawashima Takaharu、Isobe Tomohiko、Nakayama Shoji F.、Tsukahara Shinji、Maekawa Fumihiko
  • Journal Title: Environment International Volume: 138 Pages: 105662-105662
  • DOI: 10.1016/j.envint.2020.105662
  • Peer Reviewed / Open Access
• [Journal Article] Detection and Characterization of Estrogen Receptor Beta Expression in the Brain with Newly Developed Transgenic Mice (2020)
  • Author(s): Shoko Sagoshi, Sho Maejima, Masahiro Morishita, Satoshi Takenawa, Akito Otubo, Keiko Takanami, Tatsuya Sakamoto, Hirotaka Sakamoto, Shinji Tsukahara, Sonoko Ogawa
  • Journal Title: Neuroscience Volume: 438 Pages: 182-197
  • DOI: 10.1016/j.neuroscience.2020.04.047
  • Peer Reviewed / Open Access
• [Journal Article] Actions of Peripubertal Gonadal Steroids in the Formation of Sexually Dimorphic Brain Regions in Mice (2020)
  • Author(s): Morishita Masahiro、Koiso Ryoma、Tsukahara Shinji
  • Journal Title: Endocrinology Volume: 161 Issue: 6 Pages: 1-17
  • DOI: 10.1210/endocr/bqaa063
  • Peer Reviewed / Open Access
• [Journal Article] The glutamatergic system in the preoptic area is involved in the retention of maternal behavior in maternally experienced female rats (2020)
  • Author(s): Okino Eri、Morita Sayaka、Hoshikawa Yumi、Tsukahara Shinji
  • Journal Title: Psychoneuroendocrinology Volume: 120 Pages: 104792-104792
  • DOI: 10.1016/j.psyneuen.2020.104792
  • Peer Reviewed / Open Access
• [Journal Article] Sexually Dimorphic Formation of the Preoptic Area and the Bed Nucleus of the Stria Terminalis by Neuroestrogens (2020)
  • Author(s): Tsukahara Shinji、Morishita Masahiro
  • Journal Title: Frontiers in Neuroscience Volume: 14 Pages: 797-797
  • DOI: 10.3389/fnins.2020.00797
  • Peer Reviewed / Open Access
• [Journal Article] Estrogenic regulation of social behavior and sexually dimorphic brain formation. (2020)
  • Author(s): Ogawa S, Tsukahara S, Choleris E, Vasudevan N
  • Journal Title: Neuroscience and Biobehavioral Reviews Volume: 110 Pages: 46-59
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Region-specific effects of copulation on dendritic spine morphology and gene expression related to spinogenesis in the medial preoptic nucleus of male rats. (2019)
  • Author(s): Nakashima S, Morisita M, Ueno K, Tsukahara S
  • Journal Title: Psychoneuroendocrinology Volume: 108 Pages: 1-13
  • DOI: 10.1016/j.psyneuen.2019.05.025
  • Peer Reviewed / Open Access
• [Journal Article] Female-Biased Sexual Dimorphism of Corticotropin-Releasing Factor Neurons in the Bed Nucleus of the Stria Terminalis (2019)
  • Author(s): Katsuya Uchida, Hiroko Otsuka, Masahiro Morishita, Shinji Tsukahara, Tatsuya Sato, Kenji Sakimura, Keiichi Itoi.
  • Journal Title: Biology of Sex Differences Volume: 10(6) Issue: 1 Pages: 1-11
  • DOI: 10.1186/s13293-019-0221-2
  • Peer Reviewed / Open Access
• [Journal Article] Neonatal septal lesions prevent behavioral defeminization caused by neonatal treatment with estradiol in female rats (2019)
  • Author(s): Kanaya Moeko、Tsukahara Shinji、Yamanouchi Korehito
  • Journal Title: Neuroscience Letters Volume: 694 Pages: 80-85
  • DOI: 10.1016/j.neulet.2018.11.032
  • Peer Reviewed
• [Journal Article] Estrogenic regulation of social behavior and sexually dimorphic brain formation. (2018)
  • Author(s): Ogawa, S., Tsukahara, S., Choleris, E., and Vasudevan, N.
  • Journal Title: Neuroscience and Biobehavioral Reviews Volume: Oct 27 Pages: 46-59
  • DOI: 10.1016/j.neubiorev.2018.10.012
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] VGF in the Medial Preoptic Nucleus Increases Sexual Activity Following Sexual Arousal Induction in Male Rats (2018)
  • Author(s): Maejima Sho、Abe Yuta、Yamaguchi Shohei、Musatov Sergei、Ogawa Sonoko、Kondo Yasuhiko、Tsukahara Shinji
  • Journal Title: Endocrinology Volume: 159 Issue: 12 Pages: 3993-4005
  • DOI: 10.1210/en.2018-00804
  • Peer Reviewed
• [Journal Article] Temporal Expression Patterns of Genes Related to Sex Steroid Action in Sexually Dimorphic Nuclei During Puberty (2018)
  • Author(s): Kanaya Moeko、Morishita Masahiro、Tsukahara Shinji
  • Journal Title: Frontiers in Endocrinology Volume: 9 Pages: 213-213
  • DOI: 10.3389/fendo.2018.00213
  • Peer Reviewed / Open Access
• [Journal Article] Strain differences in intermale aggression and possible factors regulating increased aggression in Japanese quail. (2018)
  • Author(s): Maekawa F, Nagino K, Yang J, Htike NTT, Tsukahara S, Ubuka T, Tsutsui K, Kawashima T
  • Journal Title: General and Comparative Endocrinology Volume: 256 Pages: 63-70
  • DOI: 10.1016/j.ygcen.2017.07.025
  • Peer Reviewed
• [Journal Article] Neuronal activity in the sagittalis nucleus of the hypothalamus after ovarian steroid hormone manipulation and sexual behavior in female rat. (2018)
  • Author(s): Balabanov IE, Matsuda KI, Mori H, Yamada S, Kitagawa K, Yamamoto Y, Tsukahara S, Tanaka M
  • Journal Title: Neuroscience Letters Volume: 671 Pages: 25-28
  • DOI: 10.1016/j.neulet.2018.02.008
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Sexual experience reduces neuronal activity in the central part of the medial preoptic nucleus in male rats during sexual behavior (2018)
  • Author(s): Yamaguchi Shohei、Abe Yuta、Maejima Sho、Tsukahara Shinji
  • Journal Title: Neuroscience Letters Volume: 685 Pages: 155-159
  • DOI: 10.1016/j.neulet.2018.08.037
  • Peer Reviewed
• [Journal Article] マウスの脳内で新たに見つかった性的二型核 (2018)
  • Author(s): 塚原伸治
  • Journal Title: 比較内分泌学 Volume: 44 Pages: 7-11
  • NAID: 130006575915
• [Journal Article] Moxd1 Is a Marker for Sexual Dimorphism in the Medial Preoptic Area, Bed Nucleus of the Stria Terminalis and Medial Amygdala (2017)
  • Author(s): Tsuneoka Y and Funato H et al.
  • Journal Title: Front Neuroanat Volume: 11 Pages: 26-26
  • DOI: 10.3389/fnana.2017.00026
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Gonadal hormone-dependent sexual differentiation of a female-biased sexually dimorphic cell group in the principal nucleus of the bed nucleus of the stria terminalis in mice. (2017)
  • Author(s): Morishita M, Maejima S, Tsukahara S
  • Journal Title: Endocrinology Volume: 158 Issue: 10 Pages: 3512-3525
  • DOI: 10.1210/en.2017-00240
  • Peer Reviewed / Open Access
• [Journal Article] Sexual behavior-associated c-Fos indcuation in the sagittalis nucleus of the hypothalamus in male rat. (2017)
  • Author(s): Matsuda KI, Uchiyama K, Mori H, Maejima S, Yamaguchi S, Tanaka M, Tsukahara S
  • Journal Title: Neuroscience Letters Volume: 661 Pages: 104-107
  • DOI: 10.1016/j.neulet.2017.09.053
  • Peer Reviewed / Open Access
• [Presentation] Sexually dimorphic neural projections of calbindin-D28K neurons in the medial preoptic area of mice (2020)
  • Author(s): Morishita M, Ono K, Tsuneoka Y, Horio S, Kato S, Kobayashi K, Tsukahara S
  • Organizer: The 97th Annual Meeting of the Physiological Society of Japan（第97回日本生理学会大会）
• [Presentation] 形態学的な性差と領域特性を示すGABA作動性カルビンディンニューロンの生理機能の探索 (2020)
  • Author(s): 三塚萌理、森下雅大、小野浩太、塚原伸治
  • Organizer: 第32回日本行動神経内分泌研究会
• [Presentation] 中脳腹側被蓋野へ投射する内則視索前野のカルビンディンニューロンは勃起の制御に関与する (2020)
  • Author(s): 森下雅大、三塚萌理、恒岡洋右、塚原伸治
  • Organizer: 第32回日本行動神経内分泌研究会
• [Presentation] Sexually dimorphic neural projections of calbindin-D28K neurons in the medial preoptic area of mice. (2020)
  • Author(s): Morishita M, Ono K, Tsuneoka Y, Horio S, Kato S, Kobayashi K, Tsukahara S
  • Organizer: The 97th Annual Meeting of the Physiological Society of Japan
• [Presentation] Sexual differentiation of calbindin neuron in the preoptic area. (2019)
  • Author(s): Shinji Tsukahara
  • Organizer: The 42nd Annual Meeting of the Japan Neuroscience Society
  • Invited
• [Presentation] Female-Biased Sexual Dimorphism of Corticotropin-Releasing Factor Neurons in the Bed Nucleus of the Stria Terminalis. (2019)
  • Author(s): Uchida K, Otsuka H, Morishita M, Tsukahara S, Sato T, Sakimura K, Itoi K
  • Organizer: The 42nd Annual Meeting of the Japan Neuroscience Society
• [Presentation] Effects of sodium arsenite on proliferation and cytoskeletal gene expressions of mouse cortical astrocytes. (2019)
  • Author(s): Htike N-T-T, Maekawa F, Kobayashi S, Maejima S, Tsukahara S
  • Organizer: The 42nd Annual Meeting of the Japan Neuroscience Society
• [Presentation] A sex difference in the activity of neurons expressing calbindin-D-28K in the medial preoptic area during copulation in rats. (2019)
  • Author(s): Morishita M, Kamada A, Tsukahara S
  • Organizer: The 42nd Annual Meeting of the Japan Neuroscience Society
• [Presentation] Functional sex difference in calbindin neurons in the medial preoptic area on the control of sexual behavior in rats. (2019)
  • Author(s): Ueno K, Maejima S, Morishita M, Tsukahara S
  • Organizer: The 42nd Annual Meeting of the Japan Neuroscience Society
• [Presentation] Synergism of estrogen receptorα and androgen receptor in the regulation of male-type social behavior. (2019)
  • Author(s): Sagoshi S, Sano K, Morishita M, Tsukahara S, Agmo A, Ogawa S
  • Organizer: The 42nd Annual Meeting of the Japan Neuroscience Society
• [Presentation] マウスの分界条床核主核におけるカルビンディンニューロンの神経投射 (2019)
  • Author(s): 小野浩太、森下雅大、恒岡洋右、堀尾修平、加藤茂樹、小林和人、塚原伸治
  • Organizer: 第31回日本行動神経内分泌研究会
• [Presentation] マウスの内側視索前野に存在するカルビンディンニューロンの神経投射 (2019)
  • Author(s): 森下雅大、小野浩太、恒岡洋右、堀尾修平、加藤茂樹、小林和人、塚原伸治
  • Organizer: 第31回日本行動神経内分泌研究会
• [Presentation] ラットの性行動制御におけるカルビンディンニューロンの役割 (2019)
  • Author(s): 植野寛菜、前嶋翔、森下雅大、鎌田亜里紗、塚原伸治
  • Organizer: 第31回日本行動神経内分泌研究会
• [Presentation] ラットの性行動制御における内側視索前野のカルビンディンの役割 (2019)
  • Author(s): 植野寛菜、前嶋翔、森下雅大、鎌田亜里紗、塚原伸治
  • Organizer: 第44回日本比較内分泌学会大会およびシンポジウム
• [Presentation] マウスの内側視索前野に存在するカルビンディンニューロンの神経投射 (2019)
  • Author(s): 森下雅大、小野浩太、恒岡洋右、堀尾修平、加藤茂樹、小林和人、塚原伸治
  • Organizer: 第44回日本比較内分泌学会大会およびシンポジウム
• [Presentation] A neuronal mechanism of sexual arousal in male rats. (2019)
  • Author(s): Shinji Tsukahara
  • Organizer: The 3rd Sino-Japan Symposium on the Frontier of Behavioral Neuroendocrinology
  • Int'l Joint Research / Invited
• [Presentation] Synergism of androgen receptor and estrogen receptor alpha in the regulation of male-type social behavior. (2019)
  • Author(s): Sagoshi, S, Sano K, Morishita M, Tsukahara S, Agmo A, Ogawa S
  • Organizer: The 3rd Sino-Japan Symposium on the Frontier of Behavioral Neuroendocrinology
  • Int'l Joint Research
• [Presentation] Sex steroid-dependent sexual differentiation of a female-biased sexually dimorphic cell group in the principal nucleus of the bed nucleus of the stria terminalis in mice. (2019)
  • Author(s): Morishita M and Tsukahara S
  • Organizer: The 3rd Sino-Japan Symposium on the Frontier of Behavioral Neuroendocrinology
  • Int'l Joint Research
• [Presentation] Action mechanisms of sex steroids during puberty on sexual differentiation of the brain in mice. (2019)
  • Author(s): Morishita M and Tsukahara S
  • Organizer: The 9th Federation of the Asian and Oceanian Physiological Societies Congress (FAOPS2019)
  • Int'l Joint Research
• [Presentation] Exploring the roles of calbindin-D28K in the medial preoptic nucleus in sexual behavior of male rats. (2019)
  • Author(s): Maejima S, Morishita M, Ueno K, Kamada A, Tsukahara S
  • Organizer: The 9th Federation of the Asian and Oceanian Physiological Societies Congress (FAOPS2019)
  • Int'l Joint Research
• [Presentation] 性機能を覚醒する神経メカニズム (2018)
  • Author(s): 塚原伸治
  • Organizer: 第45回日本神経内分泌学会学術集会
  • Invited
• [Presentation] スンクスの性行動と脳の性分化に対する新生仔期性ステロイドホルモンの影響に関する検討 (2018)
  • Author(s): 小林聡美、田中相子、森下雅大、塚原伸治
  • Organizer: 第29回日本行動神経内分泌研究会
• [Presentation] 性的二型核の性差形成における思春期の性ホルモンの作用機序 (2018)
  • Author(s): 森下雅大、塚原伸治
  • Organizer: 第29回日本行動神経内分泌研究会
• [Presentation] アンドロゲン受容体とエストロゲン受容体αの共発現が雄マウスの社会行動の表出に果たす役割 (2018)
  • Author(s): 佐越祥子、佐野一広、森下雅大、塚原伸治、Agmo Anders、小川園子
  • Organizer: 第45回日本神経内分泌学会学術集会
• [Presentation] 性的二型核の性差形成における思春期の性ステロイドホルモンの作用 (2018)
  • Author(s): 森下雅大、塚原伸治
  • Organizer: 第45回日本神経内分泌学会学術集会
• [Presentation] 雄ラットの性行動における内側視索前核中心部のカルビンディンニューロンの関与 (2018)
  • Author(s): 前嶋翔、森下雅大、鎌田亜里紗、塚原伸治
  • Organizer: 第45回日本神経内分泌学会学術集会
• [Presentation] 視床下部矢状核神経細胞の雌性・雄性行動過程における活性化 (2018)
  • Author(s): 松田賢一、イヴァイロバラバノフ、内山慶、前嶋翔、山田俊児、田中雅樹、塚原伸治
  • Organizer: 第45回日本神経内分泌学会学術集会
• [Presentation] Sexual differentiation of a novel female-biased sexually dimorphic cell group in murine brain. (2018)
  • Author(s): Morishita M and Tsukahara S
  • Organizer: The 9th International Congress of Neuroendocrinology
  • Int'l Joint Research
• [Presentation] Sexual arousal-associated c-fos induction in the sagittalis nucleus of the hypothalamus. (2018)
  • Author(s): Matsuda KI, Uchiyama K, Balabanov I, Maejima S, Yamaguchi S, Yamada S, Tanaka M, Tsukahara S
  • Organizer: The 9th International Congress of Neuroendocrinology
  • Int'l Joint Research
• [Presentation] Characterization of estrogen receptor beta expressing neurons in newly developed transgenic mice. (2018)
  • Author(s): Ogawa S, Sagoshi S, Maejima S, Morisita M, Sakamoto T, Sakamoto H, Tsukahara S
  • Organizer: The 9th International Congress of Neuroendocrinology
  • Int'l Joint Research
• [Presentation] Sexually dimorphic nucleus of the preoptic area reinforces sexual motivation in male rats. (2018)
  • Author(s): Tsukahara S, Maejima S, Abe Y, Nakashima S, Yamaguchi S, Ogawa S, Kondo Y
  • Organizer: The 9th International Congress of Neuroendocrinology
  • Int'l Joint Research
• [Presentation] 新たに見つかった性的二型核の性差形成機構と生理機能 (2018)
  • Author(s): 塚原伸治
  • Organizer: KOUDOU2017
  • Invited
• [Presentation] Formation and function of female-biased sexually dimorphic cell group in male-biased sexually dimorphic nucleus. (2018)
  • Author(s): Shinji Tsukahara
  • Organizer: The 95rd Annual Meeting of the Physiological Society of Japan
  • Invited
• [Presentation] Identification of a female-biased sexually dimorphic region in a male-biased sexually dimorphic nucleus of mice and roles of neonatal testicular testosterone in sexually dimorphic formation. (2018)
  • Author(s): Morishita M, Maejima S, Tsukahara S
  • Organizer: The 95rd Annual Meeting of the Physiological Society of Japan
• [Presentation] Sex difference in neuronal activity of the ventral part of the principal nucleus of the bed nucleus of the stria terminalis (BNSTpv) in parent mice. (2018)
  • Author(s): Ohata R, Tsukahara S
  • Organizer: The 95rd Annual Meeting of the Physiological Society of Japan
• [Presentation] Investigation of gene expressions related to aggression in quail diencephalon. (2018)
  • Author(s): Maekawa F, Nagano K, Yang J, Htike NTT, Tsukahara S, Ubuka T, Tsutsui K, Kawashima T
  • Organizer: The 95rd Annual Meeting of the Physiological Society of Japan
• [Presentation] 性行動の神経制御と性ホルモンの働き (2017)
  • Author(s): 塚原伸治
  • Organizer: 第6回プロゲストーゲン研究会
  • Invited
• [Presentation] Sexual differentiation of novel sexually dimorphic nucleus of dorsal hypothalamus in mice. (2017)
  • Author(s): Shinji Tsukahara
  • Organizer: International Behavioral Neuroscience Society 2017 Annual Meeting
  • Int'l Joint Research / Invited
• [Presentation] 雄ラットの内則視索前核中心部のVGF nerve growth factor inducible (VGF)は性経験後の性的動機づけの促進に関与する (2017)
  • Author(s): 前嶋翔、内山慶、森下雅大、近藤保彦、塚原伸治
  • Organizer: 日本動物学会第88回大会
• [Presentation] 雄ラットの内則視索前核中心部に発現するVGFは交尾経験による性的動機づけの亢進に関与する. (2017)
  • Author(s): 前嶋翔、内山慶、森下雅大、近藤保彦、塚原伸治
  • Organizer: 第44回日本神経内分泌学会学術集会
• [Presentation] 雄優位な性的二型核に内在する雌優位な性差がある亜領域の性分化における性ホルモンの役割 (2017)
  • Author(s): 森下雅大、前嶋翔、塚原伸治
  • Organizer: 第44回日本神経内分泌学会学術集会