Updated on 2024/02/02

写真a

 
ORIKASA CHITOSE
 
Affiliation
Faculty of Medicine, Division of Morphological and Biomolecular Research, Associate Professor
Title
Associate Professor
Profile
「脳と行動」をテーマに養育行動を制御する神経基盤の解明をめざして研究に取り組んでいます。
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Degree

  • 農学博士 ( 東京大学 )

Research Interests

  • sexual dimorphism

  • rodent

  • maternal behavior

  • preoptic area

  • paraventricular nucleus

  • oxytocin

  • lateral hypothalamic area

  • MCH

Research Areas

  • Life Science / Neuroscience-general

  • Life Science / Basic brain sciences

Research History

  • -   Associate Professor

    2021.4

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  • Nippon Medical School   Institute for Advanced Medical Sciences   Associate Professor

    2016.4 - 2021.3

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  • Nippon Medical School   Institute for Advanced Medical Sciences   Senior Assistant Professor

    2014.4 - 2016.3

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  • Nippon Medical School   Senior Assistant Professor

    2010.4 - 2014.3

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  • Nippon Medical School   Assistant Professor

    2007.4 - 2010.3

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  • Nippon Medical School

    1995.4 - 2007.3

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Papers

  • 養育行動神経回路とその機能 Invited

    折笠千登世

    月刊細胞ー変貌する行動生物学ー   55 ( 8 )   81 - 85   2023.7

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  • Social network plasticity of mice parental behavior. Invited Reviewed

    Chitose Orikasa

    Frontiers in Neuroscience, section Neuroendocrine Science.   16   882850 - 882850   2022.6

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    DOI: 10.3389/fnins.2022.882850.

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  • Neural Contributions of the Hypothalamus to Parental Behaviour Invited Reviewed

    Chitose Orikasa

    International Journal of Molecular Sciences   22 ( 13 )   6998 - 6998   2021.6

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    Publishing type:Research paper (scientific journal)   Publisher:MDPI AG  

    Parental behaviour is a comprehensive set of neural responses to social cues. The neural circuits that govern parental behaviour reside in several putative nuclei in the brain. Melanin concentrating hormone (MCH), a neuromodulator that integrates physiological functions, has been confirmed to be involved in parental behaviour, particularly in crouching behaviour during nursing. Abolishing MCH neurons in innate MCH knockout males promotes infanticide in virgin male mice. To understand the mechanism and function of neural networks underlying parental care and aggression against pups, it is essential to understand the basic organisation and function of the involved nuclei. This review presents newly discovered aspects of neural circuits within the hypothalamus that regulate parental behaviours.

    DOI: 10.3390/ijms22136998

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  • Regulation of Morphological and Functional Aspects of Sexual Dimorphism in the Brain Invited Reviewed

    Chitose Orikasa

    Phycoendocrinology; Oxytocin and Health [Working Title]   2021.4

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    Publishing type:Part of collection (book)   Publisher:IntechOpen  

    Sexual dimorphism of the adult brain regulates sex-dependent functions including reproductive and neuroendocrine activities in rodents. It is determined by sex steroid hormones during a critical perinatal period in female and male rodents. Sex steroids act on each nuclear receptor in the brain and control different physiological and neuroendocrine functions and behaviors. Several regions of the brain show evident morphological sex differences that are involved in their physiological functions. This review addresses and focuses largely on the role of sex-dependent differences in the brain, and their crucial functions in animal models. Particularly, recent intriguing data concerning the diversity of neuronal functions and sexual dimorphism are discussed.

    DOI: 10.5772/intechopen.97470

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  • Involvement of MCH‑oxytocin neural relay within the hypothalamus in murine nursing behavior Reviewed

    Yoko Kato, Harumi Katsumata, Ayumu Inutsuka, Akihiro Yamanaka, Tatsushi Onaka, Shiro Minami, Chitose Orikasa

    Scientific Reports   11   3348   2021.1

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    DOI: 10.1038/s41598-021-82773-5

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  • Oxytocin is indispensable for conspecific-odor preference and controls the initiation of female, but not male, sexual behavior in mice. Reviewed

    Dhungel S, Rai D, Terada M, Orikasa C, Nishimori K, Sakuma Y, Kondo Y

    Neuroscience Research   148   34 - 41   2019

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    Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.neures.2018.11.008

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  • Vomeronasal signal deficiency enhances parental behavior in socially isolated male mice Reviewed

    Chitose Orikasa, Yasuhiko Kondo, Harumi Katsumata, Misao Terada, Toshio Akimoto, Yasuo Sakuma, Shiro Minami

    PHYSIOLOGY & BEHAVIOR   168   98 - 102   2017.1

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:PERGAMON-ELSEVIER SCIENCE LTD  

    We previously reported that social isolation promotes parental care in sexually naive male mice. This effect was blocked by exposure to chemosensory and auditory social signals derived from males in an adjacent compartment. In the present study, we examined whether the chemosensory signals detected in the vomeronasal organ (VNO) are involved in parental behavior by using mice deficient for a VNO-specific ion channel (Trpc2(-/-))and thus impaired in VNO-input signaling. We housed virgin homozygous Trpc2(-/-) and heterozygous Trpc2(+/-) males for 3 weeks during puberty (5-8 weeks old) alone or in groups of 3-5 males. At 8 weeks of age, the mice were placed with three pups in an observation cage and tested for parental behavior. The Trpc2(-/-) males housed under isolated conditions spent significantly longer in the vicinity of pups than did the Trpc2(-/-) males than had been group housed, whereas no isolation effect was observed in heterozygous Trpc2(+/-) males. Both Trpc2 knockout and isolation housing significantly increased the time males spent licking pups and crouching (arched back posture over pups to enable nursing), whereas only isolation housing increased the incidence of retrieval behavior. These results demonstrated that social signals transmitted not only through the VNO but also from other modalities, independent of each other, suppress the expression of parental behavior during puberty in sexually naive males. (C) 2016 Elsevier Inc All rights reserved.

    DOI: 10.1016/j.physbeh.2016.11.004

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  • Social isolation prompts maternal behavior in sexually naive male ddN mice Reviewed

    Chitose Orikasa, Kentaro Nagaoka, Harumi Katsumata, Manami Sato, Yasuhiko Kondo, Shiro Minami, Yasuo Sakuma

    PHYSIOLOGY & BEHAVIOR   151   9 - 15   2015.11

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:PERGAMON-ELSEVIER SCIENCE LTD  

    Maternal behavior in mice is considered to be sexually dimorphic; that is, females show maternal care for their offspring, whereas this behavior is rarely shown in males. Here, we examined how social isolation affects the interaction of adult male mice with pups. Three weeks of isolation during puberty (5-8 weeks old) induced retrieving and crouching when exposed to pups, while males with I week isolation (7-8 weeks old) also showed such maternal care, but were less responsive to pups. We also examined the effect of isolation during young adulthood (8-11 weeks old), and found an induction of maternal behavior comparable to that in younger male mice. This effect was blocked by exposure to chemosensory and auditory social signals derived from males in an attached compartment separated by doubled opaque barriers. These results demonstrate that social isolation in both puberty and postpuberty facilitates male maternal behavior in sexually naive mice. The results also indicate that airborne chemicals and/or sounds of male conspecifics, including ultrasonic vocalization and noise by their movement may be sufficient to interfere with the isolation effect on induction of maternal behavior in male mice. (C) 2015 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.physbeh.2015.07.007

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  • Current perspective of studies on brain sex difference

    折笠 千登世, 佐久間 康夫

    Biological science   62 ( 4 )   194 - 202   2011.7

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    Language:Japanese   Publisher:日本生物科学者協会  

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  • Similar numbers of neurons are generated in the male and female rat preoptic area in utero Reviewed

    Chitose Orikasa, Yasuhiko Kondo, Sumiko Usui, Yasuo Sakuma

    NEUROSCIENCE RESEARCH   68 ( 1 )   9 - 14   2010.9

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ELSEVIER IRELAND LTD  

    The birth date of neurons comprising the sexually dimorphic nucleus of the rat preoptic area (SDN-POA) was determined by bromodeoxyuridine (BrdU) injections at a prescribed time during the embryonic period. Calbindin immunostaining was used as a marker to identity the SDN-POA The animals were bred from dams injected with BrdU on days 14, 16 or 18 of pregnancy (fertilization defined as day 1). On day 15 after birth (PD). all offspring were euthanized and brain sections were prepared for histology. Neurogenesis in the SDN-POA began around embryonic day (ED) 14 and culminated on ED 18, whereas the preoptic neurons surrounding the SDN-POA generated earlier than did those of the SDN-POA. Although the SDN-POA was significantly larger in males than in females at PD 15, the total numbers of neurons comprising the SDN-POA were not significantly different between sexes. Similar aggregates of somatostatin mRNA-positive cells in the central portion of the SDN-POA were observed in both sexes at PD8. On PD15, the aggregates became scattered in males, whereas the aggregates in females remained congested These data suggest that sexual dimorphism in the SDN-POA results from male-specific postnatal radial spreading of cells rather than cell proliferation during embryonic neurogenesis. (C) 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

    DOI: 10.1016/j.neures.2010.05.008

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  • Estrogen Configures Sexual Dimorphism in the Preoptic Area of C57BL/6J and ddN Strains of Mice Reviewed

    Chitose Orikasa, Yasuo Sakuma

    JOURNAL OF COMPARATIVE NEUROLOGY   518 ( 17 )   3618 - 3629   2010.9

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    Immunohistochemistry using a calbindin D28k antibody revealed a marked sex difference in neuronal distribution in the central portion of the medial preoptic area in C57BL/6J and ddN strains of mice when the animals were sacrificed on D65 (D1 = the day of birth). Male mice had a distinct ellipsoidal cell aggregate, whereas females lacked such a structure. This sex difference was not observed in Nissl-stained sections. Co-localization of calbindin D28k and the neuron-specific nuclear protein NeuN confrmed that the cells in the aggregate were neurons. The aggregates were larger in males than in females in both strains. When observed on D65, males orchidectomized on D1 had smaller aggregates. However, daily injections of 2 mu g estradiol benzoate through D1-D5 as well as a single injection of 100 mu g testosterone propionate on D1 enlarged the aggregates in females, but a single injection of 100 mu g dihydrotestosterone on D1 had no effect on the female phenotype. Similar endocrine manipulations had no effects in adult animals of both sexes. Thus, the calbindin-immunoreactive cell aggregates in the preoptic area of C57BL/6J and ddN mice are homologous to the sexually dimorphic nucleus of the rat preoptic area in terms of the morphology and sex steroid-dependent organization. J. Comp. Neurol. 518:3618-3629, 2010. (C) 2010 Wiley-Liss, Inc.

    DOI: 10.1002/cne.22419

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  • Sex steroids and the establishment of the sexually dimorphic nucleus of the preoptic area Reviewed

    Chitose Orikasa, Yasuo Sakuma

    NEUROSCIENCE RESEARCH   65   S12 - S12   2009

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    DOI: 10.1016/j.neures.2009.09.1540

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  • Transient transcription of the somatostatin gene at the time of estrogen-dependent organization of the sexually dimorphic nucleus of the rat preoptic area Reviewed

    Chitose Orikasa, Yasuhiko Kondo, Yasuo Sakuma

    ENDOCRINOLOGY   148 ( 3 )   1144 - 1149   2007.3

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ENDOCRINE SOC  

    In situ hybridization detected a transient, sex-specific transcription of somatostatin gene in the central part of the rat medial preoptic nucleus, which coincides with the sexually dimorphic nucleus of the preoptic area (SDN-POA), during, but not after, the establishment of sex difference. On postnatal d 1 (day of birth), somatostatin mRNA was detected in the SDN-POA of both sexes. On d 8 through 35, the area of somatostatin mRNA-positive cells was significantly larger in males than in females. In males the area attained its maximum size on d 15 and diminished gradually thereafter. In females the area did not change in size during this period. On d 60 expression of somatostatin mRNA was low and not different between sexes. Throughout the observed period, Nissl staining and calbindin immunohistochemistry enabled visualization of the typical SDN-POA in the same region. As with Nissl staining and calbindin immunohistochemistry, somatostatin mRNA hybridization on d 15 revealed a reversal of the sexual dimorphism in the size of the SDN-POA in males that had been neonatally orchidectomized or females given estrogen as pups, showing that sex steroid milieu during the organizational period determines the area occupied by somatostatin mRNA-positive cells. Sex-specific, transient transcription of the somatostatin gene may causally relate to the estrogen-dependent organization of the SDN-POA.

    DOI: 10.1210/en.2006-1214

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  • Sexual dimorphic expression of estrogen receptor β in the rat brain

    Orikasa Chitose, Sakuma Yasuo, Shinji Hayashi

    Journal of Kyoto Prefectural University of Medicine   114 ( 6 )   347 - 358   2005.6

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  • エストロゲン受容体βの発現における性差 (特集 基礎脳科学が明かす脳の性) -- (性ホルモン受容体の脳内分布)

    折笠 千登世, 佐久間 康夫

    性差と医療   2 ( 2 )   161 - 165   2005.2

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  • Sex and region-specific regulation of oestrogen receptor in the rat hypothalamus Reviewed

    C Orikasa, Y Sakuma

    JOURNAL OF NEUROENDOCRINOLOGY   16 ( 12 )   964 - 969   2004.12

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:BLACKWELL PUBLISHING LTD  

    Sexual dimorphism in the expression of oestrogen receptor (ER)beta mRNA and protein was characterized in the rostral forebrain of the rat and its dependence on the neonatal endocrine environment was revealed. We present novel data demonstrating, in gonadectomized adult rats, that the amount of oestrogen caused a significant reduction in the number of ERbeta messages and protein in the ventromedial nucleus in both sexes, but no such effects were detected in the preoptic area or the amygdala. in gonadectomized females, more so than in males, the ventromedial nucleus of the adult rat contained a significantly larger number of ERbeta-positive neurones both in terms of ERbeta mRNA and protein. in the juvenile rat on day 14, sex difference in ERbeta expression was already observed in the ventromedial nucleus. Treatment of neonatal females with oestrogen from days 1-10 or neonatal orchidectomy of males reversed the sex difference in the ventromedial nucleus when observed on day 14, showing that the neonatal presence of oestrogen had caused irreversible masculinization of this structure. Our results suggest that sex-specific expression of ERbeta is patterned by perinatal hormone exposure: down-regulation of ERbeta caused by oestrogen in a region-specific manner.

    DOI: 10.1111/j.1365-2826.2004.01254.x

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  • Possible involvement of preoptic estrogen receptor beta positive cells in luteinizing hormone surge in the rat Reviewed

    C Orikasa, Y Sakuma

    DOMESTIC ANIMAL ENDOCRINOLOGY   25 ( 1 )   83 - 92   2003.7

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ELSEVIER SCIENCE INC  

    The anteroventral periventricular nucleus (AVPV) of the preoptic area has been implicated in the induction of spontaneous ovulation. In the AVPV, we found a striking sex difference in the distribution of estrogen receptor (ER) positive cells. In females, a significantly larger number of ER mRNA-positive cells were visualized than in males using in situ hybridization in the most medial part of the AVPV next to the ependymal lining of the third ventricle. In males, the labeled cells were dispersed into more lateral region. Immunohistochemistry revealed a similar sexual dimorphism in the ER protein. The dimorphism persisted from Day 7 to Day 60. Orchidectomy of male neonates or estrogen treatment of female pups had reversed the brain phenotype when examined on Day 14. No gross sex difference was detected in the pattern of ER expression in the medial preoptic nucleus and the bed nucleus of the stria terminals. Estrogen receptor immunoreactive cells co-localization in 83% of ER mRNA positive cells in the AVPV of adult females. Infusion of an ER antisense oligonucletide into the third ventricle resulted in a significantly longer period of successive vaginal estrus and 50% reduction in the number of ER-immunoreactive cells in the AVPV. These findings suggest an important role of ER AVPV in the female-typical estrogen-dependent induction of the luteinizing hormone surge. (C) 2003 Elsevier Science Inc. All rights reserved.

    DOI: 10.1016/S0739-7240(03)00047-X

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  • Sex difference in the expression and regulation of nitric oxide synthase gene in the rat preoptic area Reviewed

    T Ishihara, C Orikasa, T Araki, Y Sakuma

    NEUROSCIENCE RESEARCH   43 ( 2 )   147 - 154   2002.6

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    Neuronal nitric oxide synthase (nNOS) mRNA-positive cells were visualized by non-isotopic in situ hybridization histochemistry in the organum vasculosum of the lamina terminalis (OVLT) and the preoptic area (POA) in gonadectomized juvenile female and male rats. In the rostral POA (rPOA) at the level of the anteroventral periventricular nucleus, nNOS mRNA-positive cells were distributed in an inverted V-shaped area over the third ventricle and were in close proximity to cell bodies of gonadotropin-releasing hormone (GnRH)-immunoreactive neurons. In the caudal POA (cPOA) at the level of the medial preoptic nucleus, no topological association existed between GnRH and nNOS. Throughout the rPOA, both the number and the area of nNOS mRNA positive cells were significantly larger in the gonadectomized females than in the gonadectomized males. Treatment with estradiol for 2 days, followed by progesterone in the next morning, which caused an increase in serum luteinizing hormone 6 h later, induced a significant reduction of the nNOS mRNA expression in the rPOA in the female but not in the male rat at the time of sacrifice. In the OVLT and the cPOA, ovarian steroids had no effect on nNOS mRNA expression of both sexes. The results indicate that nNOS mRNA expression in the rPOA is sexually dimorphic and regulated by ovarian steroids in a sex specific manner. (C) 2002 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

    DOI: 10.1016/S0168-0102(02)00025-1

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  • Sexually dimorphic expression of estrogen receptor beta in the anteroventral periventricular nucleus of the rat preoptic area: Implication in luteinizing hormone surge Reviewed

    C Orikasa, Y Kondo, S Hayashi, BS McEwen, Y Sakuma

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   99 ( 5 )   3306 - 3311   2002.3

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:NATL ACAD SCIENCES  

    Striking sex difference was detected in the expression of estrogen receptor (ER) 0 mRNA and protein by nonisotopic in situ hybridization and immunohistochemistry in the anteroventral periventricular nucleus (AVPV) of the rat preoptic area. In females more than in males, a significantly larger number of ERbeta mRNA-positive cells were visualized in the medial-most portion of the AVPV within 50 mum from the ependymal lining of the third ventricle. Rats of 7, 14, 21, 35, and 60 days of age (d 1 = day of birth) showed the sex difference. Orchidectomy of male neonates or estrogen treatment of female pups reversed the brain phenotype when examined on d 14. In the AVPV of adult females, ERalpha immunoreactivity colocalized in 83% of ER mRNA-positive cells. Tyrosine hydroxylase immunoreactivity colocalized in 18% of ERbeta immunoreactive cells in d 21 females. infusion of an ERbeta antisense oligonucleotide into the third ventricle in the vicinity of the AVPV resulted in significantly longer days of successive estrus and a 50% reduction in the number of ERbeta-immunoreactive cells in the AVPV. These findings provide support for the hypothesis that activation of ERbeta in the AVPV is an important regulatory event in the female-typical induction of luteinizing hormone surge by estrogen.

    DOI: 10.1073/pnas.052707299

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  • 視床下部エストロゲン受容体と生殖機能

    折笠千登世, 佐久間康夫

    Clinical Neuroscience   10   43 - 46   2001

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  • Estrogen receptor alpha, but not beta, is expressed in the interneurons of the hippocampus in prepubertal rats: an in situ hybridization study Reviewed

    C Orikasa, BS McEwen, H Hayashi, Y Sakuma, S Hayashi

    DEVELOPMENTAL BRAIN RESEARCH   120 ( 2 )   245 - 254   2000.4

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    Estradiol is involved in the differentiation and plasticity of hippocampal neurons. In the CA1 region, estrogen treatment increases dendritic spines and synapse density on pyramidal cells. In the adult hippocampus, immunoreactivity for estrogen receptor alpha (ER alpha) has been reported in inhibitory interneurons, but neither in the pyramidal neurons nor in granule cells. Estrogens also mediate aspects of sexual differentiation of the hippocampus. To examine the possibility that an alteration in expression of the two types of estrogen receptors (ER alpha and ER beta) in the hippocampus underlies different roles of estrogen and/or ERs during development and in adult life, we applied non-isotopic, digoxigenin (dig)-labeled, in situ hybridization histochemistry (ISHH) for the both ER forms and examined the distribution pattern of their messages in serial, frontal sections over the postnatal period and in the adult. ER alpha mRNA expression was found scattered throughout the hippocampus especially in the hilar region of the dentate gyrus, and in the strata radiatum and pyramidale in the cornus ammonis at postnatal days (PND) 14, 21 and 35. In the hilus of the dorsal hippocampus, the density of ER alpha-labelled cells was greater in the rostro-medial aspect, while less in the lateral and the caudal region. In the ventral hippocampus the signals for ER alpha mRNA were also found in relatively high density in the hilus. No significant sex difference in distribution and intensity of the ER alpha mRNA positive cells were detected. The hippocampal distribution of ER alpha mRNA expression at PND 14 remained the same on PND 21 and 35 and in adulthood. As reported for adults, ER alpha mRNA signals appear to be in interneurons of the hippocampus but neither in the pyramidal cells nor in the dentate granular cells based on their size and location. In contrast to the result of ER alpha, no clear signals for ER beta mRNA were detected in the hippocampus across all ages examined, whereas they were clearly detected in the hypothalamus. (C) 2000 Elsevier Science B.V. All rights reserved.

    DOI: 10.1016/S0165-3806(00)00016-X

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  • Gender specific responsiveness to stress and glucocorticoids is determined by the prinatal steroid environment and 'reinforced' by gonadal secretion Reviewed

    Patchev VK, Hayashi S, Orikasa C, Almeid OF

    Stress   3   41 - 54   1999

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  • 発育期ラット海馬におけるα型エストロゲン受容体の発現 (第7回性差医学研究会) -- (各科領域における「性差医学」最近の研究)

    折笠 千登世, 佐久間 康夫, 林 しん治

    性差医学   ( 5 )   93 - 98   1999

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  • Ontogeny of gender-specific jresponsiveness to stress and glucocorticoids in the rat and its determination by the neonatal gonâdal steroid environment Reviewed

    Vladimir K. Patchev, Shinji Hayashi, Chitose Orikasa, Osborne F. X. Almeida

    Stress   3 ( 1 )   41 - 54   1999

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Taylor and Francis Ltd.  

    The neuroendocrine response to stress in the rat displays gender-specific characteristics resulting from both sex hormone-dependent organization of jieuroendocrine regulatory mechanisms and the modulatory action of circulating gonadal steroids. To define the role of gonadal steroid-mediated brain differentiation in the emergence of sex-specific differences in pituitary-adrenal function, and the necessity of physiological gonadal secretions for the manifestation of these differences, we examined the ontogeny of diurnal and stress-induced corticosterone (B) secretion, and suppressibility of the latter by dexamethasone (DEX) in intact male and female rats, and in animals that were subject to neonatal manipulations of the gonadal steroid environment (orchidectomy in males and neonatal estrogenization in females). Further, gene expression of corticosteroid receptors (MR and GR), corticotropin-releasing hormone (CRH) and arginine-vasopressin (AVP) under basal conditions, and following adrenalectomy (ADX) and chronic supplementation with high doses of B, were investigated in adult male and female rats, and individuals of both sexes which have been exposed to alterations of the gonadal steroid milieu during early development. The results demonstrate that: i) gender-specific differences in basal and stress-induced adrenocortical secretion are present at birth, but are still maleable by neonatal alterations of the gonadal steroid environment
    ii) gender-specific dichotomy in the sensitivity of the secretory stress response to glucocorticoid feedback becomes fully manifest in adulthood
    Hi) sex differences in basal adrenocortical secretion become fully expressed only in the presence of intact gonads, whereas, once established by the neonatal hormonal milieu, differential sensitivity of the stress response to glucocorticoids persists in the absence of functioning gonads
    iv) neonatal hormone manipulations alter sex-specific characteristics of CRH, AVP, MR and GR gene expression in the brain, and the changes persist in adulthood independently of gonadal secretions
    v) regulation of CRH gene expression by glucocorticoids displays gender-specific patterns which are probably established during the period of sex hormone-dependent brain organization and their manifestation does not require physiological gonadal secretions in adulthood. © 1999 OPA (Overseas Publishers Association) Amsterdam N.V. Published by license under the Gordon and Breach Publishers imprint.

    DOI: 10.3109/10253899909001111

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  • 神経内分泌の観点から見たエストロゲン受容体研究の課題 (シリ-ズ[性を探る]小特集・「下垂体2」)

    折笠 千登世, 林 〔シン〕治

    ヒュ-マンサイエンス   10 ( 2 )   48 - 56   1998.3

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  • Distribution and hormone regulation of estrogen receptor immunoreactive cells in the hippocampus of male and female rats Reviewed

    NG Weiland, C Orikasa, S Hayashi, BS McEwen

    JOURNAL OF COMPARATIVE NEUROLOGY   388 ( 4 )   603 - 612   1997.12

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    Estrogen regulates the synaptic plasticity and physiology of the hippocampus as well as learning behaviors that are mediated by the hippocampus. The density of dendritic spines and synapses, the number of N-methyl-D-aspartate (NMDA) binding sites, the levels of NMDA receptor subunit NR1 protein, muscimol binding to the gamma-amino butyric acid (GABA)(A) receptor, and levels of glutamic acid decarboxylase message in the CA1 region of the hippocampus are altered with estrogen treatment. In addition, some of these parameters exhibit sex differences in their response to estrogen treatment. To establish that estrogen can have a direct effect on the hippocampus and to determine whether or not sex differences in estrogen responsiveness are due to sex differences in estrogen receptor (ER) levels, we used immunocytochemistry with the AS409 antibody to map the location of ER-immunoreactive (ER-ir) cells in the hippocampus of male and female rats. We found that (1) the ERs appear to be in interneurons rather than pyramidal or granule cell neurons, (2) ER-ir cells are located in greatest concentration in the hilus of the dentate gyrus and the stratum radiatum of the CA1 region, (3) the density of ER-ir cells exhibits a rostral to caudal gradient in the hilus and the CA1 regions, (4) there are no sex differences in either the number or immunostaining intensity of ER-ir cells in the hippocampus, (5) the ER levels are down-regulated by estrogen in both male and female rats, and (6) the mean intensity of staining for the ER-ir cells in the hippocampus is about 25% of that in the ER-ir cells of the hypothalamus. From this, we can conclude that estrogen can have a direct effect on hippocampal neurons and that any sex differences in estrogen responsiveness is due to something other than sex differences in ER levels or function in the hippocampus. (C) 1997 Wiley-Liss, Inc.

    DOI: 10.1002/(SICI)1096-9861(19971201)388:4<603::AID-CNE8>3.0.CO;2-6

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  • Neural Control of Reproduction: Physiology and Behavior, “Developmental aspects of estrogen receptors in the rat brain Japan

    Hayashi, S. Yokosuka, M, Orikasa, C

    Scientific Societies Press, In Maeda,K. and Tsukamura,H. (eds.)   135 - 152   1997

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  • Sex differences of the brain. Roles of sex steroid receptors in sexual differentiation of the brain.

    林しん治, 横須賀誠, 折笠千登世

    Brain Med   8 ( 3 )   265 - 271   1996.9

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  • Exogenous estrogen acts differently on productionof estrogen receptor in the preoptic area and the mediobasal hypothalamic nuclei in the newborn rat. Reviewed

    Orikasa, C., Mizuno, K., and Sakuma, Y., Hayashi, S.

    Neuroscience Research   25 ( 3 )   247 - 254   1996

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    Expression of the estrogen receptor (ER) in the preoptic area (POA) and the mediobasal hypothalamus (MBH) in newborn female rats was studied by immunohistochemistry (IHC) and in situ hybridization histochemistry (ISHH). The number of ER immunoreactive (ER-IR) cells decreased and expression of ER mRNA was suppressed in the arcuate (ARH) and the ventromedial (VMH) hypothalamic nuclei by daily injections of estradiol benzoate (EB) for ten consecutive days. In contrast, in the POA, expression of ER mRNA was not suppressed by EB treatment, while the ER immunoreactivity and the number of ER-IR cells was decreased by EB treatment. Results of quantification of ER mRNA by reverse transcription-polymerase chain reaction correlated well with results from ISHH: that is: ER mRNA expression decreased in the MBH but not in the POA. Thus, estrogen affects ER gene expression differently in these two brain regions.

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  • EXPRESSION OF ESTROGEN-RECEPTOR IN THE FACIAL NUCLEUS IS SUPPRESSED BY ESTRADIOL, BUT NOT BY TESTOSTERONE, INDICATING A LACK OF REQUIREMENT FOR AROMATIZATION Reviewed

    C ORIKASA, M YOKOSUKA, S HAYASHI

    BRAIN RESEARCH   693 ( 1-2 )   112 - 117   1995.9

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    The transient expression of estrogen receptor (ER) in the ventromedial subnucleus of the facial nucleus was previously detected in the newborn rat, and the expression of ER molecules was down-regulated by daily injections of estradiol. Here we examined possible involvement of aromatization in this process. ER molecules were measured by immunohistochemistry and in situ hybridization histochemistry after daily injections of testosterone propionate (TP;100 mu g/0.02 ml) and estradiol benzoate (EB; 10 mu g/0.02 ml) in the male pups castrated within 24 h of birth. Daily injections of TP for 5 consecutive days did not suppress ER and ER mRNA in the facial nucleus, while they were both suppressed by daily injections of EB. Moreover, aromatase immunoreactivity was not detected in the facial nucleus of both castrated, TP injected and intact control males at 6 days of age. The present findings therefore suggest that ER molecules expressed transiently in the facial nucleus are not directly involved in masculine sexual differentiation of the brain in newborn rat.

    DOI: 10.1016/0006-8993(95)00723-4

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  • IMPLICATIONS OF ESTROGEN-DEPENDENT BRAIN ORGANIZATION FOR GENDER DIFFERENCES IN HYPOTHALAMO-PITUITARY-ADRENAL REGULATION Reviewed

    VK PATCHEV, S HAYASHI, C ORIKASA, OFX ALMEIDA

    FASEB JOURNAL   9 ( 5 )   419 - 423   1995.3

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    Estrogens, derived from the aromatization of testosterone in the brain, account for sex-specific organization of neural circuits controlling gonadotropin release and sexual behavior. This study examines the possible organizing role of perinatal gonadal steroids in the manifestation of known, albeit unexplained, male-female differences in basal and stress-related adrenocortical secretion. We document here the existence of gender-specific differences in the gene expression of hypothalamic corticotropin-releasing hormone (CRH), and hippocampal and hypothalamic glucocorticoid receptors (GR), diurnal corticosterone secretion, as well as in the responsiveness of CRH and GR mRNA levels to exogenous estradiol, In addition, we report that neonatal estrogenization of female rats profoundly affects several regulatory substrates of the hypothalamo-pituitary-adrenal (HPA) axis, namely, the gene expression of CRH, arginine-vasopressin (AVP) and GR in the brain, and the responsiveness of these parameters to estrogen, The neonatal treatment appeared to ''defeminize'' a number of neuroendocrine mechanisms related to HPA function; these changes were reminiscent of those observed in earlier studies on sexual differentiation of reproductive behavior and hormonal secretion, The results indicate a pivotal role for estrogens during early development for the determination of gender-specific differences in HPA function in the mature animal and demonstrate for the first time that the brain-organizing actions of gonadal steroids may extend to nonreproductive neuroendocrine axes.

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  • ESTROGEN-RECEPTOR FOUND IN THE FACIAL NUCLEUS OF THE NEWBORN RAT IS SUPPRESSED BY EXOGENOUS ESTROGEN - IMMUNO AND IN-SITU HYBRIDIZATION HISTOCHEMICAL-STUDIES Reviewed

    C ORIKASA, H OKAMURA, S HAYASHI

    DEVELOPMENTAL BRAIN RESEARCH   82 ( 1-2 )   9 - 17   1994.10

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    Expression of the messenger RNA coding estrogen receptor (ER-mRNA) was detected in the ventromedial subnucleus of the facial nucleus of the newborn rat by in situ hybridization histochemistry (ISHH). The hybridization signal in this subnucleus increased from 1 to 6 days of age, then decreased at 11 days. By immunohistochemistry (IHC) using an antiserum which detects estrogen receptor (ER) specifically, immunopositive signals were also detected in the same subnucleus of the adjacent sections. On the other hand, neither of these signals were encountered in the same subnucleus of the adult rat. Thus, the present result extend our previous work (Yokosuka and Hayashi, 1992) showing that the expression of the ER in the facial nucleus is transient. A sex difference in the expression of ER molecules was not apparent by ISHH and IHC. Moreover,,daily injections of estradiol from the day of birth suppressed the expression of ER in the subnucleus at 6 and 11 days of age. Thus, as has been detected in the mediobasal hypothalamus, ER-mRNA was revealed to be down-regulated by estrogen.

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  • Induction of oocyte-nurse cell differentiation in the ovary by the brain durig the initial stage of oogenesis in the silkworm of Bombyx mori (Lepidoptera: Bombycidae). Reviewed

    Orikasa C, Hyodo S, Urano A

    Nippon Susan Gakkashi   58   1723 - 1727   1992

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  • Induction of oocyte-nurse cell differentiation in the ovary by the brain durig the initial stage of oogenesis in the silkworm of Bombyx mori (Lepidoptera: Bombycidae). Reviewed

    Orikasa, C, Yamauchi, H, Nagasawa, H

    Appl. Entmol. Zoology   28   302 - 311   1992

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  • Cultivation of the Brain-Corpora Cardica-Corpora Allata Complex of the Silkworm, Bombyx mori and Eclosion Hormone Activity of the Cultured Organs and Medium. Reviewed

    Skakibara Y, Orikasa C, Hugo H

    J. Appl. Entomol. Zoology   31   118 - 120   1990

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  • Cultivation of the brain-corpora cardiaca-corpora allata complex of the silkworm, Bombyx mori and eclosion hormone activity of the cultured organs and medium.

    SAKAKIBARA Mika, ORIKASA Chitose, FUGO Hajime

    Japanese Journal of Applied Entomology and Zoology   34 ( 1 )   63 - 70   1990

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    In order to clarify the regulation mechanism for eclosion hormone synthesis and secretion, fundamental culture conditions for brain-corpora Cardiaca-corpora allata complexes (Br-CC-CA complexes) of the silkworm, Bombyx mori, were established. When 10 brains were placed in 3ml of CSM-2F medium, eclosion hormone activity was detected throughout the cultured periods. On the 6th day of the cultivation, the positive response for Bombyx eclosion hormone assay from the cultured brains was about 60%, and thereafter the activity decreased with the culture. Eclosion hormone activity was first detectable from the cultured medium 6 days after the cultivation. The highest eclosion hormone titer in the cultured medium was 22.5 units. It was concluded that culture conditions were not appropriate for the hormone synthesis since the hormone titer in brains and culture media was extremely low compared with those in vivo. Therefore, the culture conditions were modified for using Br-CC-CA complexes. It seemed suitable to culture 10 Br-CC-CA complexes together in 1ml of CSM-2F medium with a gentle stream of air at 25±1°C in 16 L-8 D. In these conditions, an increase of about 2-fold in eclosion hormone titer was observed in a brain during 12 day culture periods. Although the eclosion hormone activity was not detected in CC-CA and media at the initiation of culture, hormone activity in CC-CA could be detected 4 days after onset of the cultivation. Furthermore, the hormone titer in CC-CA became 2 units after 12 days cultivation. On the other hand, 55 units of hormone titer was detected in 1ml of the medium 12 days after onset of cultivation, indicating that 5.5 units of hormone were released from 1 Br-CC-CA complex. Eclosion hormone titer detected from cultured Br-CC-CA complexes and media and expressed as the titer from a single Br-CC-CA complex coincided well with the hormone titer present in 1 intact animal. Morphological changes of brain and CA were scarcely observed during 16 days culture periods in the CSM-2F medium. These results indicate that the synthesis and secretion of eclosion hormone occurred during the culture periods.

    DOI: 10.1303/jjaez.34.63

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    Other Link: http://agriknowledge.affrc.go.jp/RN/2010471990

  • STUDIES ON THE ECLOSION BEHAVIOR OF THE SILKWORM, BOMBYX-MORI (LEPIDOPTERA, BOMBYCIDAE) .5. SENSITIVITY TO ECLOSION HORMONE IN THE PHARATE-ADULTS OF THE SILKWORM Reviewed

    C ORIKASA, H FUGO

    JAPANESE JOURNAL OF APPLIED ENTOMOLOGY AND ZOOLOGY   31 ( 2 )   116 - 120   1987.5

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    DOI: 10.1303/jjaez.31.116

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  • BINUCLEATE CELLS IN THE NEURAL GLAND OF THE ASCIDIAN, HALOCYNTHIA-RORETZI (DRASCHE) Reviewed

    M OGAWA, C ORIKASA, K TERAKADO

    ZOOLOGICAL SCIENCE   2 ( 2 )   213 - 217   1985

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Misc.

  • Social isolation facilitates maternal care in both sexually naïve male and female ddN mice.

    Chitose Orikasa, Kentaro Nagaoka, Harumi Katsumata, Manami Sato, Yasuhiko Kondo, Shiro Minami, Yasuo Sakuma

    9th International Congress of Neuroendocrinology   2018.7

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  • Mouse pup retrieval and crouching behavior following social isolation in virgin male mice.

    Orikasa C, Nagaoka K, Kondo Y, Minami S, Sakuma Y

    8th International Congress of Neuroendocrinology   2014.8

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  • Neurons in the sexually dimorphic nucleus are born later in the embryonic rat brain than those in the surrounding preoptic area.

    Orikasa C, Kondo Y, Usui S, Sakuma Y

    15th Annual Meeting of the Society for Behavioral Neuroendocrinology   2011.6

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  • Sexual Dimorphism in the Preoptic Area of C57BL/6J and ddN Strains of Mice.

    Orikasa C, Sakuma Y

    7th International Congress of Neuroendocrinology   2010.7

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  • Postnatal neurogenesis does not contribute to estrogen-induced sex difference in the number of somatostatin neurons in the rat preoptic area.” 13th Annual Meeting of the Society for Behavioral Neuroendocrinology

    Orikasa C, Kondo Y, Usui S, Sakuma Y

    36th International congress of physiological Science   2009.6

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  • ONTOGENY OF SOMATOSTATIN NEURONS IN THE SEXUALLY DIMORPHIC NUCLEUS OF THE RAT PREOPTIC AREA Reviewed

    Chitose Orikasa, Yasuhiko Kondo, Sumiko Usui, Yasuo Sakuma

    JOURNAL OF PHYSIOLOGICAL SCIENCES   55   229 - 229   2009

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  • Generation of the somatostatin neurons in the sexuallydimorphic nucleus of the rat preoptic area

    Orikasa C., Kondo Y. & Sakuma Y.

    12th Annual Meeting of the Society for Behavioral Neuroendocrinology   2008.7

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  • Sex difference of somatostatin gene expression in the sexually dimorphic nucleus of the rat preoptic area

    Orikasa Chitose

    Proc Annu Meet PSJ   2008 ( 0 )   14 - 14   2008

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    Somatostatin is widely distributed in the central nervous system and the periphery, and is implicated in neuronal survival or neurogenesis. The number of somatostatin neurons is sexually dimorphic in the human or rat bed nucleus of the stria terminals. In the rat, one of the most prominent brain sex differences is found in the volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA), and which is significantly larger in the male than in the female. The difference also depends on the gonadal-steroid milieu during the critical period. In the present study, a transient, sex-specific transcription of somatostatin gene was detected by in situ hybridization in the rat SDN-POA, during the establishment of sex difference. On postnatal day 1 (day of birth), somatostatin mRNA was detected in the SDN-POA of both sexes. On days 8 through 35, the area of somatostatin mRNA-positive cells was significantly larger in males than in females. In males, the area attained its maximum size on day 15 and diminished gradually thereafter. In females, the area did not change in size during this period. On day 60, expression of somatostatin mRNA was low and not different between sexes. As with Nissl staining and calbindin immunohistochemistry, somatostatin mRNA hybridization on day 15 revealed a reversal of the sexual dimorphism in the size of the SDN-POA in males that had been neonatally orchidectomized or females given estrogen as pups. Sex-specific, transient transcription of the somatostatin gene may causally relate to the estrogen-dependent organization of the SDN-POA. &lt;b&gt;[J Physiol Sci. 2008;58 Suppl:S14]&lt;/b&gt;

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  • Transient transcription of the somatostatin gene in the sexually dimorphic nucleus of the rat preoptic area

    Orikasa Chitose, Sakuma Yasuo

    Proc Annu Meet PSJ   2007 ( 0 )   174 - 174   2007

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    Somatostatin, originally identified as a hypothalamic peptide that inhibits the secretion of pituitary growth hormone, is widely distributed in the central nervous system and the periphery, and is implicated in neuronal survival or neurogenesis. By using non-isotopic &lt;U&gt;in situ&lt;/U&gt; hybridization histochemistry, we report here that somatostatin gene is expressed transiently in the central part of the rat medial preoptic nucleus, which coincides with the sexually dimorphic nucleus of the preoptic area (SDN-POA), during, but not after, the establishment of sex difference. On postnatal day 1 (day of birth), somatostatin mRNA was detected in the SDN-POA of both sexes. On days 8 through 35, the area of somatostatin mRNA-positive cells was significantly larger in males than in females. In males, the area attained its maximum size on day 15 and diminished gradually thereafter. In females, the area did not change in size during this period. On day 60, expression of somatostatin mRNA was low and not different between sexes. Throughout the observed period, Nissl staining and calbindin immunohistochemistry enabled visualization of the typical SDN-POA in the same region. Orchidectomy of males on day 1 decreased, and administration of estradiol benzoate to females (10 &amp;micro;g in 0.02 ml sesame oil) on days 1 through 10 increased the volume of somatostatin mRNA-positive areas which corresponded to the SDN-POA, when observations were made on day 15. Sex-specific, transient transcription of the somatostatin gene may causally relate to the estrogen-dependent organization of the SDN-POA. &lt;b&gt;[J Physiol Sci. 2007;57 Suppl:S174]&lt;/b&gt;

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  • Sexually dimorphic expression of somatostatin gene in the developing preoptic area.

    Orikasa C, Kondo Y, Sakuma Y

    10th Annual Meeting of the Society for Behavioral Neuroendocrinology   2006.7

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  • Sex difference in somatostain mRNA expression in the rat SDN-POA

    Chitose Orikasa, Yasuhiko Kondo, Yasuo Sakuma

    NEUROSCIENCE RESEARCH   55   S158 - S158   2006

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  • ER beta positive neurons in the ventromedial hypothalamic nucleus project to the mesencephalic central gray

    Orikasa Chitose, Kondo Yasuhiko, Sakuma Yasuo

    Proc Annu Meet PSJ   2005 ( 0 )   S213 - S213   2005

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    ER&amp;beta; mRNA and protein were visualized in the adult rat forebrain by non-isotopic, digoxigenin-labeled in situ hybridization histochemistry and immunohistochemistry. All ER&amp;beta;-mRNA positive cells expressed ER&amp;beta; protein. In the ventromedial hypothalamic nucleus (VMN) of gonadectomized males and females, ER&amp;beta; positive cells scattered along the rostrocaudal axis with an increasing number toward the caudal, ventrolateral portion. In gonadectomized animals, females had contained a significantly larger number of ER&amp;beta;-positive cells than males. Estrogen supplement caused significant reductions in the number of ER&amp;beta; positive cells in both sexes. Infusion of a retrograde tracer, Fluoro-Gold in the midbrain central gray (CG) at the mid-collicular level labeled about 30% of ER&amp;beta; positive cells in the caudal portion of the VMN. Sex-difference in the number of ER&amp;beta;-positive cells with CG projection suggests sex-specific modulation of autonomic sensory or behavioral function of estrogen through ER&amp;beta;. &lt;b&gt;[Jpn J Physiol 55 Suppl:S213 (2005)]&lt;/b&gt;

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  • P-19 マウスの射精後性行動抑制の分子メカニズム(日本動物心理学会第65回大会発表要旨)

    近藤保彦, 保田恵子, 肖凱, 折笠千登世, 佐久間康夫

    動物心理学研究   55 ( 2 )   111 - 111   2005

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  • Sex difference in somatostatin mRNA expression in the rat preoptic area

    ORIKASA C

    Soc Neurosci Progr   761   19 - 19   2005

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  • Estrogen down-regulates estrogen receptor beta expression in the rat ventromedial hypothalamus

    Orikasa Chitose, Sakuma Yasuo

    Proc Annu Meet PSJ   2004 ( 0 )   S223 - S223   2004

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    In the preoptic area and the hypothalamus of rat brain, estrogen receptor (ER) &amp;alpha; mRNA and protein are expressed and regulated by estrogen. Here we report sex difference and estrogen-dependent, region-specific regulation of ER&amp;beta;, another major molecule which mediates estrogen action. ER&amp;beta; mRNA and protein were visualized in the rat brain, in particular, the ventromedial nucleus of the hypothalamus, preoptic area and medial amygdala of both sexes, by either non-isotopic &lt;I&gt;in situ&lt;/I&gt; hybridization or immunohistochemistry. In the ventromedial nucleus and the preoptic area of gonadectomized adult animals, a significantly larger number of neurons with ER&amp;beta; message or protein were detected in females than in males. Such sex difference was not detected in the amygdala. In the ventromedial nucleus of either sex, estrogen administration to the gonadectomized adults caused a reduction of ER&amp;beta; message or protein; no such effects were detected in the preoptic area or the amygdala. The results suggest that region-specific, ligand-dependent regulation of ER&amp;beta; in the rat brain. &lt;b&gt;[Jpn J Physiol 54 Suppl:S223 (2004)]&lt;/b&gt;

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  • Sex difference in ERbeta mRNA expression in the rat ventromedial hypothalamic nucleus.

    Orikasa C, Kondo Y, Sakuma Y

    35th SfN the Annual Meeting   2003

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  • Sexually dimorphic expression of estrogen receptor β in the anteroventral periventricular nucleus of the rat preoptic area: Implication for female sexual cyclicity.

    Orikasa C, Sakuma Y

    5th international congress of Neuroendocrinology   2002.8

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  • Sex difference in ERβ mRNA expression in the anteroventral periventricular nucleus of the rat preoptic area.

    Orikasa C, Hayashi S, McEwen B. S

    5th Annual Meeting of the Society for Behavioral Neuroendocrinology   2001.6

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  • P-375 ラット視索前野における一酸化窒素合成酵素mRNAの発現

    石原 珠紀, 折笠 千登世, 明楽 重夫, 竹下 俊行, 荒木 勤, 佐久間 康夫

    日本産科婦人科學會雜誌   53 ( 2 )   503 - 503   2001

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  • Sex difference in the developing rat forebrain.

    Orikasa C, Hayashi S, Sakuma Y

    The 78th Annual Meeting of the physiological Society of Japan.   Jpn J Physiol 50 S7   2000

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  • 内側視索前野におけるエストロゲン感受機構の性分化の特異性

    佐久間 康夫, 折笠 千登世

    自律神経 = The Autonomic nervous system   34 ( 3 )   239 - 239   1997.6

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  • ER mRNA expression in the hippocampus of the rat during development.

    Orikasa C, Hayashi H, Hayashi S

    27th SfN the Annual Meeting   23   712   1997

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  • 内側視索前野におけるエストロゲン感受機構の性分化の特異性

    佐久間 康夫, 折笠 千登世

    日本自律神経学会総会プログラム・抄録   49   52 - 52   1996.10

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  • EXPRESSION OF ESTROGEN RECEPTOR IN THE HIPPOCAMPUS IN YOUNG RATS

    HAYASHI Shinji, YOKOSUKA Makoto, ORIKASA Chitose, S. MCEWEN Bruce

    11   39 - 39   1996.8

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  • 脳の男女差“脳の性分化における性ステロイド受容体の役割

    林しん治, 横須賀誠, 折笠千登世

    Brain Medical   8   43 - 49   1996

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  • Properties of estrogen receptor (ER) including cells appearing transiantly in facial nerve nucleus of newborn rats.

    林しん治, 折笠千登世, 横須賀誠, 植田弘子

    日本動物学会大会予稿集   66th   21   1995.9

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    J-GLOBAL

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  • Exogenous estrogen acts differently on production of estrogen receptor in the preopticarea and the mediobasal hypothalamic nuclei.

    Orikasa, C, Hayashi S

    3rd International Congress of Neuroendocrinology   7   3   1994

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Presentations

  • Generation of the somatostatin neurons in the sexually dimorphic nucleus of the rat preoptic area

    Orikasa C, Kondo Y, Sakuma Y

    Hormones and Behavior SBN Annual meeting  2008.7 

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  • Sex steroid and the establishment of the sexually dimorphic nucleus of the preoptic area “How are neuroendocrine hypothalamic structure sculpted ?”

    Orikasa C

    he 32th Annual Meeting of the Japan Neuroscience Society  2009 

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  • 脳の性差形成とステロイドホルモン

    折笠千登世

    第3回日本医科大学―早稲田大学シンポジウム「成体ホメオスタシスの神経科学的神経内分泌的制御機構のupdate」  2009 

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  • Postnatal neurogenesis does not contribute to estrogen-induced sex difference in the number of somatostatin neurons in the rat preoptic area.

    Orikasa C, Kondo Y, Usui S, Sakuma Y

    Hormones and Behavior SBN Annual meeting  2009.6 

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  • Ontogeny of somatostatin neurons in the sexually dimorphic nucleus of the rat preoptic area.

    Orikasa C, Kondo Y, Usui S, Sakuma Y

    2009.7 

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  • Sex steroids and the establishment of the sexually dimorphic nucleus of the rat preoptic area.

    Orikasa C, Kondo Y, Usui S, Sakuma Y

    39th SfN the Annual Meeting  2009.10 

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  • Sexual Dimorphism in the Preoptic Area of C57BL/6J and ddN Strains of Mice.

    Orikasa C, Sakuma Y

    The 7th International Congress of Neuroendocrinology  2010.7 

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  • ラット脳視索前野性的二型核及び分界上床核2領域の非連続的神経核形成

    折笠千登世

    第17回“性と生殖”公開シンポジウム  2011 

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  • Neurons in the sexually dimorphic nucleus are born later in the embryonic rat brain than those in the surrounding preoptic area

    Orikasa C, Kondo H, Usui S, Sakuma Y

    15 th Annual Meeting of the Society for Behavioral Neuroendocrinology  2011 

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  • Mouse pup retrieval and crouching behavior following social isolation in virgin male mice

    Orikasa C, Nagaoka K, Kondo Y, Minami S, Sakuma Y

    The 8th International Congress of Neuroendo- crinology  2014 

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  • Deficiency of vemoronasal signals enhances parental behavior in socially isolated male mice.

    Orikasa C, Kondo Y, Katsumata H, Tereda M, Akimpoto T, Sakuma Y, Minami S

    2016 

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  • Social isolation facilitates maternal care in sexually naïve female ddN mice.

    Social isolation facilitates maternal care in sexually, naïve female, ddN mice

    2017 

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  • Social isolation facilitates maternal care in both sexually naïve male and female ddN mice.

    Orikasa C, Kato Y, Kondo Y, Katsmata H, Minami S

    2018 

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  • Effects of cell-specific ablation of MCH neurons on parental behavior in mice.

    Kato Y, Katsumata H, Minami S, Orikasa C

    2019 

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  • 長期の社会的隔離が性的未経験マウスの養育行動を促進する

    折笠千登世, 加藤陽子, 勝又晴美, 南史朗

    2019 

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  • ERβ mRNA expressed in the rat forebrain.

    Orikasa C, McEwen B.S, Hayashi S

    The 14the TMIN international symposium  1998 

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  • Sex difference in ERβ mRNA expression in the developing rat brain.

    Orikasa C, Sakuma Y, Hayashi S

    Brain Nose & Pituitary International Symposium  2000 

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  • Sexually dimorphic expression of estrogen receptor β in the rat preoptic area: Implication in luteinizing hormone surge

    Orikasa C.

    Workshop ‘Progress in Reproductive Physiology’ Institute of Animal Science  2002 

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  • Possible involvement of preoptic estrogen receptor beta positive cells in luteinizing hormone hormone surge.

    Orikasa C, Sakuma Y

    Environmental physiological symposium  2002 

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  • 脳のエストロゲン受容体の発達変化

    折笠千登世

    第25回日本神経科学大会サテライトシンポジウム「脳内ステロイドリセプターの今」  2002 

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  • エストロゲン受容体betaによる排卵調節

    折笠千登世

    第108回日本解剖学会総会・全国学術集会シンポジウム「ストレス、生殖、摂食の神経科学」  2003 

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  • Sex difference of somatostatin gene expression in the sexually dimorphic nucleus of the rat preoptic area.

    Orikasa C

    The 85th Annual Meeting of the Physiological Society of Japan  2008 

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Research Projects

  • 養育行動にみる養育と攻撃/無視行動における視床下部機能の役割

    Grant number:23K05858  2023.4 - 2026.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    折笠 千登世

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    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

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  • Hypothalamic neural circuit controls parental behavior in female and male mice.

    Grant number:19K12738  2019.4 - 2023.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

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    Grant amount:\4030000 ( Direct Cost: \3100000 、 Indirect Cost:\930000 )

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  • Sexually dimorphic forebrain nucleus and social bonding

    Grant number:17K08578  2017.4 - 2020.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Sakuma Yasuo

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    Grant amount:\4420000 ( Direct Cost: \3400000 、 Indirect Cost:\1020000 )

    Oxytocin (oxt) receptors in the preoptic area (POA), which include hormone-sensitive sexually dimorphic nuclus (SDN-POA), have been implicated in sexual partner preference in males in various species. In male mice with oxt knockout, preference to estrous females was lost, however, the size of the SDN-POA remained as same as in wild-type males. The observation contradicted the prevailing notion and called for a revision. In the current series of experiments, we showed (1) oxt knock-outs diminished sexual partner preference in both male and female mice; (2) a lacrimal protein in rats, cystatin-related protein 1, induces defensive response through the vomeronasal system, a major source of neural inputs to the POA; (3) ticking of the young rats, which replicated cutaneous sensory stimulation during rough-and-tumble play of the animal, established avid attachment of the animal to the experimenter: the animal would be useful in the animal assisted therapy in rehabilitation medicine.

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  • Physiological function of the rat SDN-POA analyzed by sst-siRNA recombinant adenovirus vector

    Grant number:23590285  2011.4 - 2015.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    ORIKASA Chitose, MIYAKA Koichi

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    Grant amount:\5330000 ( Direct Cost: \4100000 、 Indirect Cost:\1230000 )

    We have shown earlier that during development, somatostatin (sst) gene is transiently transcribed in neurons in the sexually dimorphic nucleus of the rat preoptic area (SDN-POA) characterized by calbindin immunoreactivity. We hypothesized that mechanisms other than apoptosis are involved in the establishment of the SDN-POA. BrdU immunoreactivity showed up in calbindin-labeled neurons in the SDN-POA of PD15 cohorts treated on 14, 16 or 18 embryonic days (ED). The number of BrdU-positive neurons was largest in animals given BrdU on 18 ED. Daily injections of BrdU during postnatal day 1-10 labeled a few calbindin-immunoreactive cells in the SDN-POA of PD15 brain of male and female rats. Next step, we analyzed the physiological function of the male rat SDN-POA by the treatments of sst-siRNA recombinant adenovirus vector and esi sst-siRNA followed by preference and sexual behavior test. Sst neurons expressed in the SDN-POA are unlikely involved in sexual behavior of male rat.

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  • Molecular mechanism for sex-specific reorganization of prosocial brain function during puberty

    Grant number:22390043  2010 - 2012

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    SAKUMA Yasuo, KATO Masakatsu, KIYAMA Yuko, KONDO Yasuhiko, ORIKASA Chitose, HAMADA Tomohiro, HAMADA Tomohiro

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    Grant amount:\18590000 ( Direct Cost: \14300000 、 Indirect Cost:\4290000 )

    In rodents, activation of estrogen receptor α (ERα) determines sexual phenotype of the brain a particular stage of ontogeny. Testosterone secreted by the testes during late gestational and neonatal periods is aromatized to form estradiol in the brain. Estradiol then masculinizes the brain through genomic activation of ERα; the lack of testosterone culminates in the female phenotype. The brain sexual phenotype determines sex-specific behavior and endocrinology in adults. We have shown that the sexual differentiation of the sexually dimorphic nucleus of the preoptic area (SDN-POA), which is larger in males than in females, is accomplished by estrogen-induced neuronal migration, by using a trait of transgenic rat. In the transgenics, neurons in the SDN-POA were labeled by fluorescent protein, EGFP. Migration was visualized by time-lapse microscopy of ex vivo slice culture of the brain. Further molecular biological experiments revealed the genomic activation of ERα culminates in pho phorylation/dephosphorylation kinetics of coffilin, which eventually regulates neuronal migration by altering actin dynamics. Recordings of neuronal activity in from this structure in the non-anesthetized, free-moving rat showed association of increased neuronal activity in males engaging in sexual interaction with females. Our observation of male-typical SDN-POA in oxytocin-ligand knock-out mice, which lacks mele-typical behavior, suggested the necessity of reassessment of the function of this structure in the future.

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  • Sex steroids and the sexually dimorphic nucleus of the rat preoptic area

    Grant number:20590238  2008 - 2010

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    ORIKASA Chiotse, SAKUMA Yasuo, HAMADA Tomohiro

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    Grant amount:\4810000 ( Direct Cost: \3700000 、 Indirect Cost:\1110000 )

    Although the SDN-POA was significantly larger in males than in females at PD15, the total numbers of neurons comprising the SDN-POA were not significantly different between sexes. Sexual dimorphism in the SDN-POA results from male-specific postnatal radial spreading of cells rather than cell proliferation during embryonic neurogenesis.

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  • INTRACELLULAR ION ENVIRONMENT DURING THE ONTOGENY AS A DETERMINANT OF SEXUAL PHENOTYPE OF RAT BRAIN

    Grant number:18390070  2006 - 2009

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    SAKUMA Yasuo, KATO Masakatsu, KIYAMA Yuko, KONDO Yasuhiko, ORIKASA Chitose, HAMADA Tomohiro

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    Grant amount:\17450000 ( Direct Cost: \14300000 、 Indirect Cost:\3150000 )

    In the rat, estrogen determines sexual phenotype of the brain, acting at a critical period as neonates. The sexual phenotype thus established persists into adulthood, both in morphology and electrophysiology. In the adults, the volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) is larger in males than in females. The anteroventral periventricular nucleus (AVPV) is packed with estrogen receptor (ER) ss-positive neurons in females but these cells scatter in the more lateral areas in males. Estrogen regulates axonal excitability of projection neurons in the ventromedial hypothalamus and those in the preoptic area in diametrically opposite directions in females but not in males. Male phenotype depends on the presence of estrogen as neonates ; the lack leads to the female phenotype. This research project focused intracellular signal cascades, which are kindled by estrogen through estrogen receptor (ER) α and culminate in neurogenesis, migration or cell death. 1) By using 5'-RACE we identified a new leader exon and untranslated internal exons in ERα gene. These exons were used for site-specific transcription of ERα ; 2) In a trait of transgenic rat, which express EGFP under the control of ERα promoter 0/B, ERα-positive neurons in the SDN-POA, but not those in the adjacent areas, were fluorescent. Time lapse movies showed the establishment of the SDN-POA as a result of neuronal migration ; 3) In another trait of transgenic rat, in which gonadotropin-releasing hormone (GnRH) neurons were tagged by EGFP, activation of GABAA_A receptors depolarized adult GnRH neurons due to their high chloride ion content ; 4) DNA microarray, PCR and Western-blot analysis demonstrated site-specific, opposite regulations of apoptosis- and migration-related genes in the SDN-POA and AVPV.

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  • Identification of Molecular Mechanisms of Estrogen-Regulated Brain Sex Differentiation

    Grant number:16086210  2004 - 2008

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Priority Areas  Grant-in-Aid for Scientific Research on Priority Areas

    SAKUMA Yasuo, ISHWAR S Parhar

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    Grant amount:\120000000 ( Direct Cost: \120000000 )

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  • Analysis of the region specific regulation of estrogen receptor a and β gene expression in the rat brain

    Grant number:16590182  2004 - 2006

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    ORIKASA Chitose, SAKUMA Yasuo

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    Grant amount:\3000000 ( Direct Cost: \3000000 )

    Estrogen plays critical role in sexual differentiation of the developing brain and sex-specific regulation of reproductive neuroendocrinology in adult. Cellular estrogen signaling is conveyed by nuclear estrogen receptors (ERs) which include the classical ERa 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 unclear, however, whether ERβ, like ERa is expressed in sex-specific manner. Furthermore, the presence of both ERs in the same neurons could alter the specificity of the transcription by forming heterodimers and might produce different responses to estrogen in different cells, depending on the ratios of ERa and ERβ. In our preivous study, we detected sex difference in the ERβ expression both in the anteroventral periventricular nucleus (AVPV) and the ventromedial nucleus of the hypothalamus (VMH), were reversed by altering neonatal steroid environment. We also studied the influence of estrogen in the adult in the expression of ERβ of the VMH, AVPV and the medial amygdala by using non-isotopic, digoxigenin-labeled in situ hybridization histochemistry. Our results suggest that sex specific expression of ERβ is patterned by perinatal hormone exposure, down-regulation of ERβ by estrogen is selected in a region specific manner in the adult.
    We also found the normal development and gonadal steroid modulation of a sex difference expression of somatostain mRNA positive cells within the sexually dimorphic nucleus of the preoptic area (SDN-POA). In the juvenile rat on day 8 and extending through day 15 analyzed, the volume of somatostain mRNA expressed nucleus was larger in males than in females. Orchidectomy of males on the day of birth decreased the volume of the somatostain mRNA-positive nucleus by day 15 and administraton of estradiol benzoate (10μg/0.02 ml in sesame oil) from days 1-5 to female increased the volume of somatostain mRNA-positive nucleus in the SDN-POA by day 15. Despite estrogen facilitates apoptotic cell death in the developing anteroventral periventricular nucleus of the preoptic area, estrogen prevents apoptotic cell death in the SDN-POA of female pups. Apoptosis prevention regulated by estrogen is a possible major role in regulating final volume of the SDN-POA. In the SDN-POA, however, we demonstrated here no estrogen receptor β in this nucleus as likely estrogen receptor a. Therefore, we propose that the sexual dimorphism and gonadal steroid modulation of somatostain is a possible involvement of regulating final volume of the SDN-POA.

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

    Grant number:14370025  2002 - 2005

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    SAKUMA Yasuo, KATO Masakatsu, KIYAMA Yuko, ORIKASA Chitose, HAMADA Tomohiro

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    Grant amount:\14600000 ( Direct Cost: \14600000 )

    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.

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  • Physiological Role of Estrogen Receptor β Positive Cells in Liteinizing hormone surge.

    Grant number:13670071  2001 - 2002

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    ORIKASA Chitose, SAKUMA Yasuo

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    Grant amount:\3300000 ( Direct Cost: \3300000 )

    In this project, we investigated the physiological role of estrogen receptor β (ERβ) in sexual differentiation of developing brain and sex specific regulation of reproductive neuroendocrinology in the adult rats. By using non-isotoic in situ hybridizaiton and immunohistochemistry, we found a strikingly sex difference expression of the ERβ in the anteroventral periventricular nucleus (AVPV) of the rat preoptic area. In females more than in males, a significantly of larger number ERβ mRNA positive cells were visualized in the medial portion of the AVPV within 50 μm form the ependymal surface of the third ventricle. Orchidectomy of male neonates or estrogen treatment of female pups reversed the brain phenotype when examined on day 14. In the AVPV of adult females, ERα immunoreactivity colocalized in 83% of ERβ mRNA-positive cells.
    Infusion of ERβ antisense oligonucleotide into the third ventricle in the vicinity of the AVPV resulted in significantly longer days of successive estrus and a 50% reduction in the number of ERβ-immunoreactive cells in the AVPV. These findings provide support for the hypothesis that activation of ERβ in the AVPV is an important regulatory event in the female-typical induction of luteinizing hormone surge by estrogen. We further examine the interaction between ERβ and ERα in the regulation of luteinizing hormone surge by estrogen by using oligonucleotide infusion into the AVPV now.

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  • トランスジェニックラットにおけるエストロゲン受容体陽性ニューロンの選択的破壊

    Grant number:12878155  2000 - 2001

    日本学術振興会  科学研究費助成事業 萌芽的研究  萌芽的研究

    佐久間 康夫, 折笠 千登世, 木山 裕子, 加藤 昌克

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    Grant amount:\2100000 ( Direct Cost: \2100000 )

    エストロゲンは脳の特定領域に分布するエストロゲン受容体(ER)陽性ニューロンを介して生殖内分泌や生殖行動・攻撃行動などを調節する。我々はこれまで、雌ラットの生殖行動を調節する脳内神経回路の研究を進め、エストロゲンの作用に明らかな性差があり、また脳内で部位特異性があることを明かにした。性差や部位特異性は、ER発現の雌雄差、あるいはER活性化に続く転写機序の違いと考えられる。エストロゲンはα受容体(ERα)、1996年Gustafssonらによりクローニングされたβ受容体(ERβ)、さらに膜レベルで未知の機構を介して作用する。生殖行動・攻撃行動の調節にERαが不可欠であることは、ERαノックアウトマウス(Korachら、1993)で示されている。そこで、本研究計画では、これまで我々が雌ラットの誘惑行動とロードーシス反射のそれぞれの調節に決定的な役割を演じている内側視索前野と視床下部腹内側核のERα陽性ニューロンのイムノトキシン法による選択的破壊を目指した。ERαタンパクの遺伝子上流には複数の転写制御領域があり、時期あるいは部位特異的なERα発現に関わると考えられる。kこれまでにERα遺伝子の2kb上流のプロモータP1と、さらに1kb上流のプロモータP0のそれぞれに蛍光タンパクの遺伝子を結合した融合遺伝子を作成し、ラット胚に導入してP0が視床下部や大脳辺縁系のER陽性ニューロンや腎近位尿細管、子宮筋層で使われていることを明らかにした。さらに大脳皮質や海馬など、成熟ラット脳ではERαを認めない脳部位に、生後10日令前後で一過性発現を認めた。現在これら予期しなかった興味ある現象の解明を進めており、本計画の実施には遅れを生じている。ラットにおけるERα陽性ニューロンの蛍光タンパクによる標識は世界的に先例のない先駆的成果である。ERβについては脳内発現に性差を認め、その意義を検討して米国科学アカデミー紀要(2002年2月)に発表したことが特筆される。

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

    Grant number:10480227  1998 - 2000

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B).  Grant-in-Aid for Scientific Research (B).

    SAKUMA Yasuo, ORIKASA Chitose, KIYAMA Yuko, KATO Masakatsu

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    Grant amount:\8500000 ( Direct Cost: \8500000 )

    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 knockout 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.

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  • Sex Hormone - Mediated Differentiation of Neuroendocrine System

    Grant number:09044245  1997 - 1998

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for international Scientific Research

    HAYASHI Shinji, ORIKASA Chitose, HAYASHI Hiroshi, ALVES Stephen, MCEWEN bruce, WEILANF Nancy

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    Grant amount:\4600000 ( Direct Cost: \4600000 )

    Involvement of sex steroid hormones such as estrogen and androgen in development and determination of neuroendocrine functions has been well established . In this project , we examined distribution of receptor signals for these steroid hormones in the central and peripheral nervous systems in the developing rat brain by immunohistochemistry ( IHC ) and by in situ hybridization histochemistry ( ISHH ) . The following points were revealed by a series of experiments : (1) The immunoreactivities ( ir ) for estrogen receptor a (Era ) were detected in those regions that are related to reproductive functions , such as the preoptic area , the hypothalamic arcuate nucleus , ventrolateral part of the hypothalamic ventromedial nucleus , and the medial amygdala nucleus ; (2) There was clear sex difference in the expression of Era , stronger in the female than the male , in the specific regions wherearomatase - ir was detected . This observation supports the concept that androgen of the testicular origin is converted into estrogen , and then suppresses Era expression ( down - regulation ) ; (3) Era signals were also detected in the regions such as in the cerebral cortex , the hippocampus , the midbrain central gray , although they were rather scattered but clearly . The Era signals in the hippocampus and the midbrain central gray were in the interneurons ; (4) We also detected Era - ir signals in the dorsal root ganglia where they were colocalized with the calcitonin generelated peptide ( CGRP ) . The finding suggests estrogen is involved in regulation of CGRP expression .

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  • Steroid Hormone Receptor-Containing Neurons and Differentiation of Neuroendocrine Functions

    Grant number:09640799  1997 - 1998

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    HAYASHI Shinji, ORIKASA Chitose, HAYASHI Hiroshi

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    Grant amount:\3100000 ( Direct Cost: \3100000 )

    Role of neurons that contain steroid hormone receptors, such as estrogen or androgen receptors in the development and differentiation of the brain was analyzed. By using immunohistochemistry (IHC), in situ hybridization histochemistry (ISHH) and reverse transcriptase-polymerase chain reaction (RT-PCR), we have already disclosed that estrogen receptor alpha (ERalpha) is expressed in the preoptic region, the hypothalamus and the amygdala in the rat brain. Moreover, we have disclosed ERalpha is also detected in the hylar region of the hippocampus both by IHC and ISHH.They were located sporadically in the polymorphic neurons of the hylus and granular cells of the cornus. No distinct sex difference was detected. In addition, androgen receptor immunoreactivity was detected selectively in the ventral premammillary nucleus that is located in the posterior region of the hypothalamus. The androgen receptor immunoreactivity in this nucleus increased by administration of androgen. Since no aromatase that converts testosterone into estradiol was detected in this nucleus, direct action of androgen on the neurons of this nucleus was suggested. On the other hand, a new kind of estrogen receptor that was found recently in the rat prostate and named as ERbeta is also detected in the brain. We also confirmed the expression of ERbeta in the rat brain by IHC and ISHH.

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  • 『ラット脳内エストロゲン受容体ニュウロンの分化と機能の獲得』

    Grant number:08640853  1996

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    林 しん治, 折笠 千登世, 林 洋, 横須賀 誠

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    Grant amount:\1700000 ( Direct Cost: \1700000 )

    脳内の性ステロイドホルモン受容体の分布と遺伝子発現について検討した。われわれは、免疫組織化学(IHC)、インシチュウハイブリダイゼーション組織化学(ISHH)および逆転写酵素ポリメラーゼ連鎖反応法(RT-PCR)によって、エストロゲン受容体(ER)がラット脳内の視東前野、視床下部諸核、扁桃体等に検出されることを明らかにしていたが、さらにIHCによって、ついでISHHによって、海馬の歯状回多形細胞層および海馬角顆粒層に散在的に分布していることを明らかにした。エストロゲンやプロゲステロンの性ステロイドホルモンが、海馬角錐体細胞の形態変化に影響を持ち、その活性を変化さしめるとの報告がある。したがって、錐体細胞に対するERの作用は、歯状回多形細胞層および海馬顆粒層に存在する介在ニュウロンを経由しているものと推論した。海馬組織におけるERmRNAの発現は、さらにRT-PCRによっても確認した。さらに、脳内に存在する性ステロイド転換酵素であるアロマターゼの働きによって、アンドロゲンを原料として作られたエストロゲンが脳の分化に働くとする考えが一般的ではあるが、アンドロゲン自体の独立の作用を検討する目的で、アンドロゲン受容体を認識する抗血清を用いてラット脳のIHCを行ったところ、視床下部の腹側前乳頭核に特異的に検出されアンドロゲンの投与によってその染色性が増強することを見いだした。また、この神経核にはアロマターゼが検出されなかったことから、アンドロゲンによる直接的な効果が想定された。

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  • 新生仔ラットの脳内エストロゲン受容体アイソフォームの生理的機能の解析

    Grant number:07740640  1995

    日本学術振興会  科学研究費助成事業  奨励研究(A)

    折笠 千登世

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    Grant amount:\1000000 ( Direct Cost: \1000000 )

    本研究では、脳内のエストロゲン受容体タンパク(ER)にいくつかの変異型が存在し、かつその機能が異なる可能性があるので、解析を行った。当該研究者は、これまで、発生成長に伴う正常型ERの発現調節の機構に注目し検討し、ERタンパクの出現の程度が雌雄で異なり、雄での発現は雌に比べて有意に低値を示すことを観察した。一方、ER mRNAの発現については、ERタンパクが減少するにもかかわらずER mRNAの発現は低下しない脳内領域が存在する事実を見出した。この現象は脳内領域における変異型遺伝子の発現の差に起因する可能性が考えられたので、変異型ERの解析を行った。その結果、ERの変異型であるDelta4(ER-D4)が新生仔ラットの脳に発現している事実を見出した。本年度は、これらの観察に基づいて解析を進め、次の結果を得た。
    (1)ER-D4の発現は、正常型の発現と比べると少なく、1/10程度であった。RNase protection assayによる定量解析の結果、雌雄間及び脳の領域間での発現の量はほぼ等しかった。これらの事実から、ERタンパクが減少しているにもかかわらずER mRNAの高い値が検出された現象はER-D4によるものではないことが示唆された。
    (2)次に、D4以外にER-D5及びER-D7の発現を新生仔ラット脳で検出した。これらの、変異型の発現量はER-D4と同様に低い値であった。
    (3)また、他の変異型ERの可能性を調べるために、PCR等の増幅条件を変え検索を進め、正常型の存在を示すバンドと、正常型よりも分子量の少ないバンドが検出された。PCR/Southern法により解析を進めた結果、低分子量のバンドは正常型と同様にER-cRNAプローブとhybridizeすることが明らかになった。現在、低分子量のERの塩基配列の検索を行い、新種のisoformであるか否かについて検討している。さらに、雌雄間及び脳の領域間で発現量の違いがあるかについて解析を進めている。
    以上の結果の一部は、第4回国際神経科学大会(IBRO, Kyoto,9-14,July,1995:Abstract, C2..41,pp240)で発表した。

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  • 『周生期ラットの脳内に出現するエストロゲン受容体の生物学的な意義』

    Grant number:07640893  1995

    日本学術振興会  科学研究費助成事業  一般研究(C)

    林 しん治, 折笠 千登世, 横須賀 誠

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    Grant amount:\2200000 ( Direct Cost: \2200000 )

    脳の性分化に関連する3つのタンパクである、アンドロゲン受容体・エストロゲン受容体・アロマターゼの脳内分布について遺伝子発現とタンパクの出現との両面から解析を行った。エストロゲン受容体の出現の形式には胎生期から新生仔期に限って一過性に出現する例(顔面神経核内側亜核・大脳皮質第一次聴覚野)と、新生仔期に出現する脳内領域に成熟後も検出される例(視床下部内諸核・視束前野・扁桃体・中脳灰白質等)の2種類に分けられることが明らかになった。エストロゲン受容体とアロマターゼの免疫組織化学を併用することによって、後者の領域にはアロマターゼが存在するが、前者の領域にはアロマターゼは検出されなかった。また、ラットの胎生期から新生仔期にかけて雄動物の精巣が分泌するアンドロゲンは、アロマターゼの働きによって転換されたエストロゲンによって引き起こされると考えられるので、脳の性分化が生じる脳内部域は後者の領域であることが示唆された。さらに、エストロゲン受容体はそのリガンドであるエストロゲンによって一般に抑制的調節を受けていることが知られているので、エストロゲン投与後のエストロゲン受容体の変化を免疫組織化学によるタンパクを検出し、またインシチュウハイブリダイゼーション組織化学(ISHH)および逆転写酵素ポリメラーゼ連鎖反応法(RT-PCR)を用いて遺伝子発現の量を検討することによって、この両者が並行的に推移するかどうかを解析した。タンパク量の変化と遺伝子発現とは視床下部正中基底部では並行的であったが、視束前野では、エストロゲン投与によってタンパクは減少していたが遺伝子発現にはほとんど変化が見られなかった。この現象は、エストロゲンが脳に作用して神経内分泌調節を行う際に、その脳内領域によって、受容体発現に対する異なる調節機構が働くことを示唆している。

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  • ESTROGEN RECEPTOR DETECTED IN THE FACIAL NUCLEUS OF NEWBORN RATS.

    Grant number:05804050  1993 - 1994

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for General Scientific Research (C)

    HAYASHI Shinji, ORIKASA Chitose, OKAMURA Hiroaki

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    Grant amount:\1800000 ( Direct Cost: \1800000 )

    Distribution and ontogeny of estrogen receptor (ER) -containing neurons in the newborn rat brain was examined. Neurons containing ER were classified into two types, i.e.,
    (1) Adult-type : the ER neurons appear in the same regions in the newborn as those in the adult ;
    (2) Newborn-type : the ER appears transiently only during the fetal to newborn period. The adult-type was observed in the preoptic nucleus, in the bed nucleus of the stria terminalis, in the hypothalamic arcuate, ventromedial and periventricular nuclei, in the midbrain central gray, in the lateral habenular nucleus, and medial and cortical nuclei of the amygdala. On the other hand, the newborn-type appears only in the ventromedial subnucleus of the facial nucleus and the layr 5 of the primary auditory cortex. Estrogen administration decreases ER immunoreactivity in the both types of ER.ER mRNA expression was detected by in situ hybridization in both cases. However, the area where former group was found contains aromatase immunoreactivity, which indicates androgen is converted to estradiol, while that for the latter does not. Sex difference was found only the former group. Thus, ER directly related to sex differentiation of the brain was suggested as the former (adult-type), while the latter (newborn-type) might be related to stimulating effects of estrogen in the developing brain. By retrograde track-tracing, double immunohistochemical staining of ER and choline acetyltransferase, and electron microscopic immunocytochemistry, the cells which contain ER transiently in the newborn life were suggested as immature motoneurons.

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