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2005 Fiscal Year Final Research Report Summary

Cellular physiological bases of sex-specific estrogen actions on the brain

Research Project

Project/Area Number 14370025
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental physiology (including Physical medicine and Nutritional physiology)
Research InstitutionNippon Medical School

Principal Investigator

SAKUMA Yasuo  Nippon Medical School, Grad Sch Med, Professor, 大学院・医学研究科, 教授 (70094307)

Co-Investigator(Kenkyū-buntansha) KATO Masakatsu  Nippon Medical School, Faculty of Medicine, Associate Professor, 医学部, 助教授 (90143239)
KIYAMA Yuko  Nippon Medical School, Faculty of Medicine, Assistand Professor, 医学部, 講師 (60234390)
ORIKASA Chitose  Nippon Medical School, Faculty of Medicine, Research Associate, 医学部, 助手 (20270671)
HAMADA Tomohiro  Nippon Medical School, Faculty of Medicine, Research Associate, 医学部, 助手 (90312058)
Project Period (FY) 2002 – 2005
Keywordsestrogen receptor alpha / promoter transgenic rat / sexually dimorphic nucleus / EGFP / medial preoptic area / stria terminalis / immunohistochemistry / membrane receptor
Research Abstract

Transgenic rats expressing enhanced green fluorescent protein (EGFP) under the control of an estrogen receptor (ER) alpha promoter were generated to tag ERalpha-positive neurons in the brain. Two transgenes, one containing sequences for promoter A and DsRed and the other containing sequences for promoter 0/B and EGFP, were injected simultaneously into Wistar rat zygotes. Twenty-two founders with both transgenes were identified. Ten lines of these founders expressed the EGFP tag in the brains of their first filial generation, whereas none similarly expressed the DsRed tag. In two lines selected for the brightness of the EGFP fluorescence in their brains, tagged cells showed essentially the same patterns. Tagged cells were in the preoptic area (POA), bed nucleus of the stria terminalis (BNST), hypothalamic arcuate nucleus and medial amygdala. ERalpha-immunoreactive neurons were identified in all of these structures by immunohistochemistry. In ovariectomized females, approximately 75% of the EGFP-fluorescent cells in the POA-BNST were immunoreactive for ERalpha. In the POA-BNST, ovariectomy increased the number of EGEP-immunopositive cells and estrogen supplementation reversed this effect, indicating that the promoter 0/B is involved in estrogen-induced downregulation of ERalpha. EGFP was also present in cells in the cerebral cortex and hippocampus, which have not previously been associated with endocrine regulation. Conversely, only a few cells were tagged in the hypothalamic ventromedial nucleus, which contained many ERalpha-immunoreactive neurons. This discrepancy could have arisen as a result of differential promoter usage.

  • Research Products

    (49 results)

All 2006 2005 2004 2003 2002

All Journal Article (48 results) Book (1 results)

  • [Journal Article] The medial amygdala controls coital access of female rats : A possible involvement of emotional resuonsiveness.2006

    • Author(s)
      Kondo Y, Sakuma Y
    • Journal Title

      Japanese Journal of Physiology 55(6)

      Pages: 345-353

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The medial amygdala controls coital access of female rats : A possible involvement of emotional responsiveness.2005

    • Author(s)
      Kondo Y, Sakuma Y
    • Journal Title

      Japanese Journal of Physiology 55(6)

      Pages: 345-353

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Cloning and functional analysis of promoters of three GnRH genes in a cichlid.2005

    • Author(s)
      Kitahashi T, Sato H, Sakuma Y, PARHAR IS
    • Journal Title

      Biochemical and Biophysical Research communications 36(2)

      Pages: 536-543

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The olfactory organ modulates gonadotropin-releasing hormone types and nest-building behavior in the tilapia Oreochromis niloticus.2005

    • Author(s)
      Uchida H, Ogawa S, Harada M, Matushita M, Iwata M, Sakuma Y, PARHAR IS
    • Journal Title

      Journal of Neurobiology 65(1)

      Pages: 1-11

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Visualizing forebrain-specific usage of an estrogen receptor alpha promoter for receptor downregulation in the rat.2005

    • Author(s)
      Hamada T, Wada-Kiyama Y, Sakuma Y
    • Journal Title

      Molecular Brain Research 139(1)

      Pages: 42-51

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Localization of the three GnRH types and GnRH receptors in the brain of a cichlid fish : Insights into their neuroendocrine and neuromodulator functions.2005

    • Author(s)
      Soga T, Ogawa S, MILLAR RP, Sakuma Y, PARHAR IS
    • Journal Title

      Journal of Comparative Neurology 487(1)

      Pages: 28-41

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Nonmammalian gonadotropin-releasing hormone molecules in the brain of promoter transgenic rats.2005

    • Author(s)
      PARHAR IS, Soga t, Ogawa S, PFAFF DW, Sakuma Y
    • Journal Title

      Proceedings of the National Academy of Sciences of the United States of America 102(16)

      Pages: 5880-5885

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Differential regulation of female rat olfactory preference and copulatory pacing by the lateral septum and medial preoptic area.2005

    • Author(s)
      XIAO K, Kondo Y, Sakuma Y
    • Journal Title

      Neuroendocrinology 81(1)

      Pages: 56-62

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Three GnRH receptor types in laser captured single cells of the cichlid pituitary display cellular and functional heterogeneity2005

    • Author(s)
      PARHAR IS, Ogawa S, Sakuma Y
    • Journal Title

      Proceedings of the National Academy of Sciences of the United States of America 106(2)

      Pages: 2204-2209

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Cloning and functional analysis of promoters of three GnRH genes in a Cichlid.2005

    • Author(s)
      Kitahashi T, Sato H, Sakuma Y, Parhar IS
    • Journal Title

      Biochemical and Biophysical Research Communications 336(2)

      Pages: 536-543

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Visualizing brebrain-specific usage of an estrogen receptor alpha promoter for recentor down regulation in the rat.2005

    • Author(s)
      Hamada T, Wada-Kiyama Y, Sakuma Y
    • Journal Title

      Molecular Brain Research 139(1)

      Pages: 42-51

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Surgical removal of the olfactory epithelium modulates reproductive behaviors and gonadotropin-releasing hormone (GnRH) subtypes in tilapia oreochromis nioticus.2005

    • Author(s)
      Uchida H, Ogawa S, Harada M, Matushita M, Iwata M, Sakuma Y, Parhar IS
    • Journal Title

      Journal of Neurobiology 65(1)

      Pages: 1-11

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Immunocytochemical localization of gonadotropin-releasing hormone receptor subtypes in the developing brain of Cichlid fish.2005

    • Author(s)
      Soga T, Ogawa S, Millar RP, Sakuma Y, Parhar IS
    • Journal Title

      Journal of Comparative Neurology 487(1)

      Pages: 28-41

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Nonmammalian forms of gonadotropin-releasing hormone molecules in the brain of promoter transgenic rats.2005

    • Author(s)
      Parhar IS, Soga T, Ogawa S, Ogawa S, Pfaff DW, Sakuma Y
    • Journal Title

      Proceedings of the National Academy of Sciences of the United States of America 102(16)

      Pages: 5880-5885

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Differential regulation of female rat olfactory preference and copulatory pacing by the lateral septum and medial preoptic area.2005

    • Author(s)
      Xiao K, Kondo Y, Sakuma Y
    • Journal Title

      Neuroendocrinology 81(1)

      Pages: 56-62

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Three GnRH receptor types in laser captured single cells of the cichlid pituitary display cellular and functional heterogeneity.2005

    • Author(s)
      Parhar IS, Ogawa S, Sakuma Y
    • Journal Title

      Proceedings of the National Academy of Sciences of the United States of America 102(6)

      Pages: 2204-2209

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Sex and region-specific regulation of oestrogen receptor beta in the rat hypothalamus.2004

    • Author(s)
      Orikasa C, Sakuma Y
    • Journal Title

      Journal of Neuroendocrinology 16(6)

      Pages: 964-969

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Sex-specific effects of gonadal steroids on conspecific odor preference in the rat.2004

    • Author(s)
      XIAO K, Kondo Y, Sakuma Y
    • Journal Title

      Hormones and Behavior 46(3)

      Pages: 356-361

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Expressional regulation of neuronal and cancer-related geges by estrogen in adult female rats.2004

    • Author(s)
      RHO JY, Wada-Kiyama Y, Onishi Y, Kiyama R, Sakuma Y
    • Journal Title

      Endocrine Research 30(2)

      Pages: 257-267

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Laser-captured single digoxigenin-labeled neurons of gonadotropin-releasing hormone types reveal a novel G protein-coupled receptor(Gpr54) during maturation in cichlid fish2004

    • Author(s)
      PARHAR IS, Ogawa S, Sakuma Y
    • Journal Title

      Endocrinology 145(8)

      Pages: 3613-3618

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Expression profiling of the estrogen responsive genes for evaluation of estrogen activity among natural estrogens and industrial chemicals using a customized DNA microarray2004

    • Author(s)
      Terasaka S et al. 15中9番目
    • Journal Title

      Environmental Health Perspectives Toxicogenomics 112(7)

      Pages: 773-781

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] High expression of the R-type voltage-gated Ca^2+-dependent GnRH release in GT1-7 cells2004

    • Author(s)
      Watanabe M, Sakuma Y, Kato M
    • Journal Title

      Endocrinology 145(5)

      Pages: 2375-2383

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Sex-specific effects of gonadal asteroids on conspecific odor preference in the rat.2004

    • Author(s)
      Xiao K, Kondo Y, Sakuma Y
    • Journal Title

      Hormones and Behavior 46(3)

      Pages: 356-361

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Expressional regulation of neuronal and cancer-related genes by estrogen in adult female rats.2004

    • Author(s)
      Rho JY, Wada-Kiyama Y, Onishi Y, Kiyama R, Sakuma Y
    • Journal Title

      Endocrine Research 30(2)

      Pages: 257-267

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Laser-captured single digoxigenin-labeled neurons of gonadotropin-releasing hormone types reveal a novel G protein-coupled receptor (Gpr54) during maturation in cichlid fish.2004

    • Author(s)
      Parhar IS, Ogawa S, Sakuma Y
    • Journal Title

      Endocrinology 145(8)

      Pages: 3613-3618

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Expression profiling of the estrogen responsive genes for evaluation of estrogen activity among natural estrogens and industrial chemicals using a customized DNA microarray.2004

    • Author(s)
      Terasaka S, Aita Y, Inoue A, Hayashi S, Nishigaki M, Aoyagi K, Sasaki H, Wada-Kiyama Y, Sakuma Y, Akaba S, Tanaka J, Sone H, Yonemoto J, Tanji M, Kiyama R
    • Journal Title

      Environmental Health Perspectives Toxicogenomics 112(7)

      Pages: 773-781

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] High expression of the R-type voltage-gated Ca^<2+> channel and its involvement in Ca^<2+>-dependent GnRH release in GT1-7 cells.2004

    • Author(s)
      Watanabe M, Sakuma Y, Kato M
    • Journal Title

      Endocrinology 145(5)

      Pages: 2375-2383

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Possible involvement of preoptic estrogen receptor beta positive cells in luteinizing hormone surge in the rat2003

    • Author(s)
      Orikasa C, Sakuma Y
    • Journal Title

      Domestic Animal Endocrinology 25(1)

      Pages: 83-92

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Characterization of voltage-gated calcium currents in gonadotropin-releasing hormone neurons tagged with green fluorescent protein in rats2003

    • Author(s)
      Kato M, Ui-Tei K, Watanabe M, Sakuma Y
    • Journal Title

      Endocrinology 144(11)

      Pages: 2118-5125

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] FSH and LH-beta subunits in the preoptic nucleus : Ontogenic expression in teleost2003

    • Author(s)
      PARHAR IS, Soga T, Ogawa S, Sakuma Y
    • Journal Title

      General and Comparative Endocrinology 132(3)

      Pages: 369-378

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Single-cell real-time quantitative PCR of immunofluorescently identified neurons of GnRH subtypes in cichlid fish.2003

    • Author(s)
      PARHAR IS, Ogawa S, Hamada T, Sakuma Y
    • Journal Title

      Endocrinology 144(8)

      Pages: 3297-3300

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Ghrelin gene in cichlid fish is modulated by sex and development.2003

    • Author(s)
      PARHAR IS, Sato H, Sakuma Y
    • Journal Title

      Biochemical and Biophysical Research Communications 305(1)

      Pages: 169-175

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Oestrogen-induced vigorous mounting in female rats carrying hypothalamic knife cuts.2003

    • Author(s)
      Ohnishi H, Kondo Y, Sakuma Y
    • Journal Title

      Journal of Neuroendocrinology 15(6)

      Pages: 602-606

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Activation of accessory olfactory bulb neurons during copulatory behavior after deprivation of vomeronasal inputs in male rats.2003

    • Author(s)
      Kondo Y, Sudo T, Tomihara K, Sakuma Y
    • Journal Title

      Brain Research 962(1/2)

      Pages: 232-236

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Possible involvement of preoptic estrogen receptor beta positive cells in luteinizing hormone surge in the rat.2003

    • Author(s)
      Orikasa C, Sakuma Y
    • Journal Title

      Domestic Animal Endocrinology 25(1)

      Pages: 83-92

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Characterization of voltage-gated calcium currents in gonadotropin-releasing hormone neurons tagged with green fluorescent protein in rats.2003

    • Author(s)
      Kato M, Ui-Tei K, Watanabe M, Sakuma Y
    • Journal Title

      Endocrinology 144(11)

      Pages: 5118-5125

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] FSH and LH-beta subunits in the preoptic nucleus : Ontogenic expression in teleost.2003

    • Author(s)
      Parhar IS, Soga T, Ogawa S, Sakuma Y
    • Journal Title

      General and Comparative Endocrinology 132(3)

      Pages: 369-378

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Single-cell real-time quantitative PCR of immunofluorescently identified neurons of GnRH subtypes in cichlid fish.2003

    • Author(s)
      Parhar IS, Ogawa S, Hamada T, Sakuma Y
    • Journal Title

      Endocrinology 144(8)

      Pages: 3297-3300

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Ghrelin gene in cichlid fish is modulated by sex and development.2003

    • Author(s)
      Parhar IS, Sato H, Sakuma Y
    • Journal Title

      Biochemical and Biophysical Research Communications 305(1)

      Pages: 169-175

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Ligand-dependent transcriptional enhancement by DNA curvature between two half motifs of the estrogen response element in the human estrogen receptor alpha gene.2002

    • Author(s)
      Li XM, Onishi Y, Kuwabara K, Rho JY, Wada-Kiyama Y, Sakuma Y, Kiyama R
    • Journal Title

      Gene 294(1/2)

      Pages: 279-290

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 3',5'-cAMP augments intracellular Ca^2+ concentration and gonadotropin-releasing hormone (GnRH) release in immortalized GnRH neurons in an Na^+-dependent manner.2002

    • Author(s)
      Kaneishi K, Sakuma Y, Kobayashi H, Kato M
    • Journal Title

      Endocrinology 143(11)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Spatio-temporal expression of GnRH receptor subtypes in gonadotropes, somatotropes and lactotropes in the cichlid fish.2002

    • Author(s)
      PARHAR IS, Soga T, Sakuma Y, MILLAR RP
    • Journal Title

      Journal of Neuroendocrinology 14(8)

      Pages: 657-665

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Sexually dimorphic expression of estrogen receptor b in the anteroventral periventricular nucleus of the rat preoptic area : Implication in luteinizing hormone surge.2002

    • Author(s)
      Orikasa C, Kondo Y, Hayashi S, McEwen BS, Sakuma Y
    • Journal Title

      Proceedings of the National Academy of Sciences of the United States of America 99(5)

      Pages: 3306-3311

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Sex differences in the expression and regulation of nitric oxide synthase gene in the rat preoptic area.2002

    • Author(s)
      Ishihara T, Orikasa C, Araki T, Sakuma Y
    • Journal Title

      Neuroscience Research 43(2)

      Pages: 147-154

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Ligand-dependent transcriptional enhancement by DNA curvature between two half motifs of the estrogen response element in the human estrogen receptor alpha gene.2002

    • Author(s)
      Li XM, Onishi Y, Kuwabara K, Rho JY Wada-Kiyama Y, Sakuma Y, Kiyama R
    • Journal Title

      Gene 294(1/2)

      Pages: 279-290

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] 3',5'-Cyclic adenosine monophosphate augments intracellular Ca^<2+> concentration and gonadotropin-releasing hormone (GnRH) release in immortalized GnRH neurons in an Na^+-dependent manner.2002

    • Author(s)
      Kaneishi K, Sakuma Y, Kobayashi H, Kato M
    • Journal Title

      Endocrinology 143(11)

      Pages: 4210-4217

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Spatio-temporal expression of GnRH receptor subtypes in gonadotropes, somatotropes and lactotropes in the cichlid fish.2002

    • Author(s)
      Parhar IS, Soga T, Sakuma Y, Millar RP
    • Journal Title

      Journal of Neuroendocrinology 14(8)

      Pages: 657-665

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Sex differences in the expression and regulation of nitric oxide synthase gene in the rat ureontic area.2002

    • Author(s)
      Ishihara T, Orikasa C, Araki T, Sakuma Y
    • Journal Title

      Neuroscience Research 43(2)

      Pages: 147-154

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] 脳の性分化(山内兄人, 新井康允 編 分担執筆)2005

    • Author(s)
      佐久間康夫
    • Publisher
      裳華房
    • Description
      「研究成果報告書概要(和文)」より

URL: 

Published: 2007-12-13  

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