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2000 Fiscal Year Final Research Report Summary

Physiological property of estrogen-HEADreceptor positive hypothalamic neurons visualized in transgenic rats

Research Project

Project/Area Number 10480227
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Neuroscience in general
Research InstitutionNippon Medical School

Principal Investigator

SAKUMA Yasuo  Nippon Medical School, Professor, 医学部, 教授 (70094307)

Co-Investigator(Kenkyū-buntansha) ORIKASA Chitose (佐藤 千登世)  Nippon Medidal School, Research Associate, 医学部, 助手 (20270671)
KIYAMA Yuko  Nippon Medical School, Assistant Professor, 医学部, 講師 (60234390)
KATO Masakatsu  Nippon Medical School, Associate Professor, 医学部, 助教授 (90143239)
Project Period (FY) 1998 – 2000
KeywordsESTROGEN RECEPTOR α / TRANSGENIC RAT / FLUORESCENT-PROTEIN GENE / BENT DNA / IN SITU HYBRIDIZATION / IMMUNOCYTOCHEMISTRY / NO SYNTHASE / ESTROGENRECEPTOR β
Research Abstract

Estrogens are involved in both endocrine and behavioral sex differentiation during brain development and sex-specific regulation of reproductive neuroendocrinology and behavior in adulthood. Cellular estrogen signaling is conveyed by nuclear estrogen receptors (ER) which include the classical ERα as well as the recently cloned ERβ. Both ERs are expressed in the preoptic area (POA), hypothalamus, limbic structures, which have been implicated in the regulation of reproduction. It is controversial, however, whether ERβ is expressed in sex-specific manner like ERα. Co-localization of the two ERs in identical neurons, which would alter the specificity of the transcription by forming heterodimers and produce variable responses to estrogen in different cells depending on the ratios of ERα and ERβ they contain, is also yet to be established.
Disruption of either ERα or ERβ by gene targeting affects various aspects of reproduction. Female and male ERα knockout mice are inflertile and ERβ knockou … More t females have a reduced fecundity. Anovulation and hemorrhagic or polycystic ovary are present in either the ERα or ERβ knockout females. The syndrome is due, at least partially, to the central mechanism for the secretion of gonadotropin-releasing hormone (GnRH), because several regimens that decrease gonadotropin secretion ameliorate the defects. Negative feedback action of estrogen on gonadotropin secretion is compromised in ERα-disrupted female and male mice, but progesterone receptor can be induced by estrogen in the POA of male castrates, presumably through ERβ. The major caveat associated with the use of ER knockout mice, however, is that the two ERs may interact to modulate transcriptional activity in certain cells, making separate identification of the action of ERα and ERβ difficult.
Estrogen-induced progesterone receptors act as a neuronal transcription factor which triggers GnRH surge in the female rat by altering synthesis or activity of neurotransmitters involved in the regulation of GnRH neurons. Progesterone receptors in the anteroventral periventricular nucleus (AVPV) of the POA may be particularly important. The AVPV is sexually dimorphic with over 3 times as many dopaminergic neurons in the female rat compared with males. The AVPV also contains sexually dimorphic populations of peptidergic neurons or glutamate receptor subunits, and has been implicated in the female-specific ovulatory release of GnRH with its direct projections to GnRH neurons. Indeed, small lesions confined to this region block the cyclic release of gonadotropins in the female rat and culminates in an anovulatory, persistent estrous state. Injections of progesterone receptor antisense oligonucleotides into the third ventricle adjacent to the AVPV blocks the induction of the receptor protein and prevents luteinizing-hormone surge.
We found a striking sex difference in the ERβ expression in the AVPV.Neonatal steroid status altered the sexual phenotype. ERβ mRNA co-localized in 84% of estrogen ERα immunoreactive cells, and may be dopaminergic in nature. Infusion of ERβ antisense oligonucleotides into the third ventricle adjacent to the AVPV diminished ERβ protein and produced constant vaginal diestrus. Less

  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Orikasa C,McEwen BS,Hayashi H,Sakuma Y,Hayashi S: "Estrogen receptor α, but not β, is expressed in hippocampal intemeurons in prepuberal rats.."Developmental Brain Research. 120(2). 245-254 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kato A,Sakuma Y: "Neuronal activity in female rat preoptic area associated with sexually motivated behavior."Brain Research. 862(1/2). 90-102 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Parhar IS,Soga T,Sakuma Y: "Thyroid hormone and estrogen regulate brain region-specific messenger ribonucleic acids.."Endocrinology. 141(5). 1618-1626 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chiba H,Nakamura M,Iwata M,Sakuma Y,Yamauchi K,Parhar IS: "Development and differentiation of gonadotropin hormone-releasing hormone neuronal systems.."General and Comparative Endocrinology. 114. 449-459 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kondo Y,Tomihara K,Sakuma Y: "Sensory requirement for non-contact penile erection in the rat."Behavioral Neuroscience. 113(5). 1062-1070 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wada-Kiyama Y,Kuwabara K,Sakuma Y,Onishi Y: "Localization of curved DNA and its association with nucleosome phasing in the promoter region of."FEBS Letters. 444. 117-124 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 佐久間康夫: "脳科学大事典"甘利俊一,外山敬介 編集 朝倉書店. (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 佐久間康夫(編集): "内分泌生理学講義"丸善株式会社. (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishihara T, Orikasa C, Araki T, Sakuma Y: "Sex differences in the expression and regulation of nitric oxide synthase mRNA in the rat preoptic area"Proceedings of the National Academy of Science of the USA. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakajima Y, Uchiyama M, Sakuma Y, Kato M: "Acetylcholine increases intracellular Ca^<2+> in the rat pituitary folliculo-stellate cells in primary culture"American Journal of Physiology : Regulatory, Intergrative & Comparative Physiology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Parhar IS, Tosaki H, Sakuma Y, Kobayashi M: "Sex differences in the brain of goldfish : Gonadotropin-releasing hormone and vasotocinergic neurons"Neuroscience. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miura T, Kondo Y, Akimoto M, Sakuma Y: "Electromyography of male rat perineal musculature during the implementation of copulatory behavior"Urologia Internationalis. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Uchiyama M, Nakajima Y, Sakuma Y, Kato M: "Purinergic regulation of intracellular Ca^<2+> concentration of rat pituitary folliculo-stellate cells in primary culture"Journal of Neuroendocrinology. 13(4). 378-385 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kato A, Sakuma Y: "Neuronal activity in female rat preoptic area associated with sexually motivated behavior"Brain Research. 862(1/2). 90-102 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Orikasa C, McEwen BS, Hayashi H, Sakuma Y, Hayashi S: "Estrogen receptor α, but not β, is expressed in hippocampal interneurons in prepuberal rats : In situ hybridization study"Developmental Brain Research. 120(2). 245-254 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Du J, Sudo T, Sakuma Y, Kato M: "Angiotensis II increases intracellular Ca^<2+> concentration in folliculo-stellate cells of the rat anterior pituitary in primary culture"Brain Research. 859(1). 167-168 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Parhar IS, Soga T, Sakuma Y: "Thyroid hormone and estrogen regulate brain region-specific messenger ribonucleic acids encoding three gonadotropin-releasing hormone genes in sexually immature male fish"Oreochromis Niloticus. Endocrinology. 141(5). 1618-1626 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kato M, Sakuma Y: "The effect of GHRP-6 on the intracellular Na^+ concentration of rat pituitary cells in primary culture"Journal of Neuroendocrinology. 11. 795-800 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chiba H, Nakamura M, Iwata M, Sakuma Y, Yamauchi K, Parhar IS: "Development and differentiation of gonadotropin hormone-releasing hormone neuronal systems and testes in the Japanese eel (Anguilla japonica)"General and Comparative Endoctinology. 114. 449-459 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kondo Y, Tomihara K, Sakuma Y: "Sensory requirement for non-contact penile erection in the rat."Behavioral Neuroscience. 113(5). 1062-1070 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Wada-Kiyama Y, Kuwabara K, Sakuma Y, Onishi Y, Trifonov EN, Kiyama R: "Localization of curved DNA and its association with nucleosome phasing in the promoter region of the human estrogen receptor α gene"FEBS Letters. 444. 117-124 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Parhar IS, Soga T, Sakuma Y: "Quantitative in situ hybridization of three gonadotropin-releasing hormone-encoding mRNAs in castrated and progesterone-treated male tilapia"General and Comparative Endocrinology. 112(3). 406-414 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Parhar IS, Sooa T, Ishikawa Y, Nagahama Y, Sakuma Y: "Neurons synthetizing gonadotropin-releasing hormone mRNA subtypes have multiple developmental origins in the mcdaka"Journal of Comparative Neurology. 401(2). 217-226 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Soga T, Sakuma Y, Parhar IS: "Testosterone differentially regulates expression of GnRH messenger RNAs in the terminal nerve, preoptic and midbrain of male tilapha"Molecular Brain Research. 60(1). 13-20 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tashiro S, Kondo Y, Sakuma Y: "Temporal coincidence between the excitation of ventromedial hypothalamic efferents and the induction of lordosis reflex in ovariectomized estrogen-primed rats"Endocrine Journal. 45(4). 519-528 (1998)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2002-03-26  

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