2021/07/12 更新

写真a

タケウチ サカエ
竹内 栄
TAKEUCHI Sakae
所属
自然科学学域 教授
職名
教授
外部リンク

学位

  • 理学博士

研究キーワード

  • 生物形態・構造

  • Morphology

  • Structure of Organism

研究分野

  • ライフサイエンス / 分子生物学

  • ライフサイエンス / 動物生理化学、生理学、行動学

  • ライフサイエンス / 形態、構造

学歴

  • 東北大学   Graduate School, Division of Natural Science  

    - 1990年

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  • 東北大学    

    - 1990年

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    国名: 日本国

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  • 東北大学   理学部   生物学

    - 1985年

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    国名: 日本国

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  • 東北大学   Faculty of Science  

    - 1985年

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所属学協会

 

書籍等出版物

  • 黒色素胞刺激ホルモン(MSH)とその受容体

    ストレスとホルモン(ホルモンの分子生物学シリーズNo.5),日本比較内分泌学会編,学会出版センター  1997年 

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MISC

  • Pheomelanin production in the epidermis from newborn agouti mice is induced by the expression of the agouti gene in the dermis.

    PIGMENT CELL RESEARCH   17 (5): 506-514   2004年

  • alpha-melanocyte-stimulating hormone stimulates prolactin secretion through melanocortin-3 receptors expressed in mammotropes in the mouse pituitary

    R Matsumura, C Takagi, T Kakeya, K Okuda, S Takeuchi, S Takahashi

    NEUROENDOCRINOLOGY   78 ( 2 )   96 - 104   2003年8月

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    記述言語:英語   出版者・発行元:KARGER  

    The intermediate lobe of rodent pituitaries is involved in the regulation of prolactin (PRL) secretion from the anterior lobe. In a previous study, we demonstrated the stimulatory effect of a-melanocyte-stimulating hormone (alpha-MSH) on PRL release and the expression of melanocortin-3 receptors (MC3-Rs) in cultured mouse pituitary cells. The aim of the present study was to clarify whether a-MSH directly stimulates PRL release through the MC3-Rs by determining the cell type of MC3-R-expressing cells in the mouse pituitary anterior lobe. Northern blot analysis revealed a 2.7-kb transcript for MC3-R mRNA in the anterior and neurointermediate lobes of pituitary glands of adult male and female mice. Dual cellular localization of MC3-R mRNA and PRL or growth hormone (GH) in the mouse pituitary glands was performed by in situ hybridization analysis of MC3-R mRNA followed by immunocytochemical detection of PRL or GH. MC3-R mRNA was detected in most mammotropes and some somatotropes. alpha-MSH increased PRL release and stimulated DNA replication in mammotropes, and these effects were blocked by SHU9119, an antagonist of MC3-R and MC4-R. These results indicate that a-MSH stimulates PRL release and proliferation of mammotropes through MC3-Rs, and suggest that a-MSH from intermediate lobes can regulate mammotrope functions in the mouse pituitary. Copyright (C) 2003 S. Karger AG, Basel.

    DOI: 10.1159/000071965

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  • Remarkable synteny conservation of melanocortin receptors in chicken, human, and other vertebrates

    HB Schioth, T Raudsepp, A Ringholm, R Fredriksson, S Takeuchi, D Larhammar, BP Chowdhary

    GENOMICS   81 ( 5 )   504 - 509   2003年5月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    The melanocortin receptors (MCR) belong to the superfamily of G-protein-coupled receptors that participate in both peripheral and central functions, including regulation of energy balance. Genomic clones of the five chicken (GGA) MCRs were isolated and used to find the chromosomal location of each of the loci. The genes encoding MC2R and MC5R mapped to the middle part of the long arm of chromosome 2 (GGA2q22-q26) and MC4R proximally on the same chromosome arm, close to the centromere (2q12). This arrangement seems to be conserved on chromosome 18 in the human (HSA18). The MC1R and MC3R genes mapped to different microchromosomes that also appear to share homology with the respective human localization. The conserved synteny of the MC2R, MC5R, and MC4R cluster in chicken (GGA2), human (HSA18), and other mammals suggests that this cluster is ancient and was formed by local gene duplications that most likely occurred early in vertebrate evolution. Analysis of conserved synteny with mammalian genomes and paralogon segments prompted us to predict an ancestral gene organization that may explain how this family was formed through both local duplication and tetraploidization processes. (C) 2003 Elsevier Science (USA). All rights reserved.

    DOI: 10.1016/S0888-7543(03)00028-4

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  • Association of feather colour with constitutively active melanocortin 1 receptors in chicken

    MK Ling, MC Lagerstrom, R Fredriksson, R Okimoto, NI Mundy, S Takeuchi, HB Schioth

    EUROPEAN JOURNAL OF BIOCHEMISTRY   270 ( 7 )   1441 - 1449   2003年4月

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    記述言語:英語   出版者・発行元:BLACKWELL PUBLISHING LTD  

    Seven alleles of the chicken melanocortin (MC) 1 receptor were cloned into expression vectors, expressed in mammalian cells and pharmacologically characterized. Four of the clones e(+R), e(+B&D), e(wh)/e(y), E-Rfayoumi gave receptors to which melanocortin stimulating hormone (alpha-MSH) bound with similar IC50 values and responded to alpha-MSH by increasing intracellular cAMP levels in a dose-dependent manner. Three of the cMC1 receptors; e(b), E and E-R, did not show any specific binding to the radioligand, but were found to be constitutively active in the cAMP assay. The E and E-R alleles are associated with black feather colour in chicken while the e (b) allele gives rise to brownish pigmentation. The three constitutively active receptors share a mutation of Glu to Lys in position 92. This mutation was previously found in darkly pigmented sombre mice, but constitutively active MC receptors have not previously been shown in any nonmammalian species. We also inserted the Glu to Lys mutation in the human MC1 and MC4 receptors. In contrast with the chicken clones, the hMC1-E94K receptor bound to the ligand, but was still constitutively active independently of ligand concentration. The hMC4-E100K receptor did not bind to the MSH ligand and was not constitutively active. The results indicate that the structural requirements that allow the receptor to adapt an active conformation without binding to a ligand, as a consequence of this E/K mutation, are not conserved within the MC receptors. The results are discussed in relationship to feather colour in chicken, molecular receptor structures and evolution. We suggest that properties for the 'E92K switch' mechanism may have evolved in an ancestor common to chicken and mammals and were maintained over long time periods through evolutionary pressure, probably on closely linked structural features.

    DOI: 10.1046/j.1432-1033.2003.03506.x

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  • Fasting differentially regulates expression of agouti-related peptide, pro-opiomelanocortin, prepro-orexin, and vasoactive intestinal polypeptide mRNAs in the hypothalamus of Japanese quail

    D Phillips-Singh, Q Li, S Takeuchi, T Ohkubo, PJ Sharp, T Boswell

    CELL AND TISSUE RESEARCH   313 ( 2 )   217 - 225   2003年

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    記述言語:英語   出版者・発行元:SPRINGER-VERLAG  

    Research in mammals has established the existence of a neuronal network that lies within the hypothalamus and that regulates energy homeostasis. However, it is unknown whether this system has been evolutionarily conserved. The objective of the present study was therefore to examine the influence of the agouti-related peptide (AGRP), pro-opiomelanocortin (POMC), prepro-orexin, and vasoactive intestinal polypeptide (VIP) genes on energy balance in birds by quantifying the effect of a 24-h fast on their expression in the hypothalamus of the Japanese quail. In situ hybridization revealed strong signals for AGRP and POMC mRNAs in the infundibular nucleus (IN), for prepro-orexin in the lateral hypothalamic area (LHy) and periventricular hypothalamic nucleus, and for VIP in the LHy. POMC mRNA was co-localized with alpha-melanocyte-stimulating hormone-like immunoreactivity in individual IN neurons. Compared with the ad-libitum-fed state, a 24-h fast resulted in a 2.2-fold increased expression of AGRP mRNA in the IN. However, fasting did not induce changes in POMC, prepro-orexin, or VIP mRNAs. The results suggest an involvement of the central melanocortin system in the regulation of energy balance in birds, as in mammals. In contrast, orexins in birds may be primarily involved in the control of physiological functions other than energy homeostasis.

    DOI: 10.1007/s00441-003-0755-8

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  • Gene expression and the physiological role of transforming growth factor-alpha in the mouse pituitary

    ZOOLOGICAL SCIENCE   20 (1): 83-89   2003年

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  • IGF-I regulates pro-opiomelanocortin and GH gene expression in the mouse pituitary gland

    JOURNAL OF ENDOCRINOLOGY   178 (1): 71-82   2003年

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  • Epidermal growth factor and transforming growth factor-alpha stimulate the proliferation of mouse uterine stromal cells

    ZOOLOGICAL SCIENCE   20 (5): 639-645   2003年

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  • Avian melanocortin system: alpha-MSH may act as an autocrine/paracrine hormone - A minireview

    ANNALS OF THE NEW YORK ACADEMY OF SCIENCES   994: 366-372   2003年

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  • Neurons expressing neruopeptide Y mRNA in the infrndibualr hypothalamus of Japanese quaio are activated by fasting and co-express agouri-related protein mRNA.

    Molecular Brain Research   100, 31-42   2002年

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  • Intrapituitary regulatory system of mammotrophs in the mouse

    Sumio Takahashi, S. Sharma, S. Oomizu, J. Honda, S. Takeuchi

    Archives of Physiology and Biochemistry   110 ( 1-2 )   34 - 41   2002年

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    記述言語:英語  

    Estrogen stimulates the proliferation of pituitary cells, in particular mammotrophs. The present study was designed to clarify involvement of transforming growth factor α (TGF-α) in the estrogen-induced growth of mouse pituitary cells in vitro. Anterior pituitary cells obtained from ICR male mice were cultured in a primary, serum-free culture system. Proliferation of pituitary cells was detected by monitoring the cellular uptake of a thymidine analogue, bromodeoxyuridine. Secretory cell types were immunocytochemically determined. Treatment with TGF-α (0.1 and 1 ng/ml) for 5 days stimulated cell proliferation. Since TGF-α binds to the epidermal growth factor (EGF)-receptor, this action may be exerted through this receptor. Estradiol-17β (E2, 10-9M) stimulated proliferation of mammotrophs. RG-13022, an EGF receptor inhibitor, reduced the cell proliferation induced by EGF or E2, showing that the EGF receptor was involved in this induction of mammotroph growth. Treatment with TGF-α antisense oligodeoxynucleotide (ODN) inhibited the cell proliferation induced by E2, but treatment with EGF antisense ODN did not. Dual detection of TGF-α mRNA and growth hormone by in situ hybridization and fluorescenceimmunocytochemistry demonstrated that TGF-α mRNA was detected in most somatotrophs. Our recent RT-PCR analysis revealed that E2 stimulated TGF-α-mRNA and EGF-receptor mRNA expression. These results indicate that TGF-α produced in somatotrophs mediates the stimulatory effect of estrogen on pituitary cell proliferation in a paracrine manner, and that EGF-receptor expression is stimulated by estrogen. These findings indicate that intrapituitary cell-to-cell interaction plays an important role in the control of pituitary secretory cells.

    DOI: 10.1076/apab.110.1.34.895

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  • Hepatocyte growth factor is a rehulator in the proliferation of microvascular endothelial cells in bovine corpus luteum.

    Journal of Reproduction and Development   48, 49-55   2002年

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  • Induction of mammotroph development by a combination of epidermal growth factor,insulin,and estradiol-17β in the rat tumor GH3 cells.

    Zoological Science   19, 789-795   2002年

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  • Identification of avian alpha-melanocyte-stimulating hormone in the eye: temporal and spatial regulation of expression in the developing chicken

    K Teshigawara, S Takahashi, T Boswell, Q Li, S Tanaka, S Takeuchi

    JOURNAL OF ENDOCRINOLOGY   168 ( 3 )   527 - 537   2001年3月

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    記述言語:英語   出版者・発行元:SOC ENDOCRINOLOGY  

    The presence and possible physiological roles of alpha -melanocyte-stimulating hormone (alpha -MSH) in the peripheral tissues of birds have not been established. By a combination of RT-PCR, immunocytochemistry and in situ hybridization, we have examined alpha -MSH expression in the eye of the chicken during development. In the 1-day-old chick, alpha -MSH was expressed in the retinal pigment epithelial (RPE) cells, and also at a lower level in the cone cells. The melanocortin receptor subtypes, CMC1, CMC4 and CMC5, were expressed in the layers of the choroid and the neural retina, but not in the RPE cells. It is probable that the RPE cells secrete alpha -MSH to exert paracrine effects on the choroid and neural retina. During embryonic development, alpha -MSH immunoreactivity in the RPE cells was initially detected at embryonic day 10, and increased in intensity as development proceeded. No cone cells were stained with anti-alpha -MSH antiserum in any of the embryonic stages tested. The immunoreactivities for two prohormone convertases, PC1 and PC2, were co-localized to the RPE cells with a pattern of staining similar to that of alpha -MSH. Despite containing alpha -MSH immunoreactivity, the RPE cells in 1-day-old chicks expressed no immunoreactivity for the endoproteases. Furthermore, in a 3-day-old chick, proopiomelanocortin mRNA was detectable by in situ hybridization only in the, photoreceptor layer and not in the RPE cells. These results suggest that the RPE cells and the cone cells are intraocular sources of alpha -MSH in the embryonic and postnatal life of the chicken respectively. Embryonic expression of alpha -MSH in the RPE cells implies a possible role for the peptide in ocular development.

    DOI: 10.1677/joe.0.1680527

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  • Expression and action of hepatocyte growth factor in bovine endometrial stromal cells in vitro

    Molecular Reproduction and Development   60, 472-480   2001年

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  • Identivication of a novel GH isoform:A possivle ling getween GH and melanocotrin systems in the devoloping chicken eye.

    Endocrinology   142, 5158-5166   2001年

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  • Epidermal growth factor stimulates proliferation of mouse uterine epithelial cells in primary culture

    M Shiraga, N Komatsu, K Teshigawara, A Okada, S Takeuchi, H Fukamachi, S Takahashi

    ZOOLOGICAL SCIENCE   17 ( 5 )   661 - 666   2000年7月

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    記述言語:英語   出版者・発行元:ZOOLOGICAL SOC JAPAN  

    Epidermal growth factor (EGF) is one of growth factors that are thought to mediate the stimulatory effects of estrogen on the proliferation of uterine epithelial cells. The present study was attempted to obtain direct evidence for the mitogenic effects of EGF on uterine epithelial cells, and to prove that EGF and EGF receptors are expressed in these cells. Mouse uterine epithelial cells were isolated from immature female mice and cultured with or without EGF for 5 days. EGF (1 to 100 ng/ml) significantly increased the number of uterine epithelial cells, and the maximal growth (141.9+/-8.3% of controls) was obtained at a dose of 10 ng/ml. In addition, EGF (0.1 to 100 ng/ml) increased the number of DNA-synthesizing cells immunocytochemically detected by bromodeoxyuridine uptake to the nucleus. Northern blot analysis revealed that the uterine epithelial cells expressed both EGF mRNA (4.7 kb) and EGF receptor mRNAs (10.5, 6.6, and 2.7 kb) These results suggest that the proliferation of uterine epithelial cells is regulated by the paracrine and/ or autocrine action of EGF. Our previous study demonstrated the mitogenic effect of IGF-I on uterine epithelial cells. To examine whether the EGF- and IGF-I signaling act at the same level in the regulation of the proliferation of uterine epithelial cells, the cultured cells were simultaneously treated with IGF-I and EGF. IGF-I was found to additively stimulate the mitogenic effects of EGF, suggesting that the EGF-induced growth of uterine epithelial cells is distinct from IGF-l-induced growth.

    DOI: 10.2108/zsj.17.661

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  • Transforming growth factor-alpha stimulates proliferation of mammotrophs and corticotrophs in the mouse pituitary

    S Oomizu, J Honda, S Takeuchi, T Kakeya, T Masui, S Takahashi

    JOURNAL OF ENDOCRINOLOGY   165 ( 2 )   493 - 501   2000年5月

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    記述言語:英語   出版者・発行元:SOC ENDOCRINOLOGY  

    Oestrogen stimulates the proliferation of pituitary cells. The present study was designed to clarify the involvement of transforming growth factor-alpha (TGF-alpha) in the oestrogen-induced growth of mouse pituitary cells in vitro. Anterior pituitary cells obtained from ICR male mice were cultured in a primary serum-free culture system. Proliferation of pituitary cells was detected by monitoring the cellular uptake of bromodeoxyuridine. Secretory cell types were immunocytochemically determined. Treatment with TGF-alpha (0.1 and 1 ng/ml) for 5 days stimulated cell proliferation. Since TGF-alpha binds to the epidermal growth factor (EGF) receptor, this action may be exerted through the EGF receptor. Oestradiol-17 beta (OE2, 10(-9) M) stimulated mammotrophic and corticotrophic cell proliferation. RG-13022, an EGF receptor inhibitor, inhibited the cell proliferation induced by EGF or OE2, showing that the EGF receptor was involved in the growth response in mammotrophs and corticotrophs. Treatment with antisense TGF-alpha oligodeoxynucleotide (ODN) inhibited the cell proliferation induced by OE2, but treatment with antisense EGF ODN did not. RT-PCR analysis revealed that OE2 stimulated TGF-alpha mRNA and EGF receptor mRNA expression. These results indicate that TGF-alpha mediates the stimulatory effect of oestrogen on the pituitary cell proliferation in a paracrine or autocrine manner, and that EGF receptor expression is stimulated by oestrogen.

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  • Widespread expression of Agouti-related protein (AGRP) in the chicken: a possible involvement of AGRP in regulating peripheral melanocortin systems in the chicken

    S Takeuchi, K Teshigawara, S Takahashi

    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH   1496 ( 2-3 )   261 - 269   2000年4月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    Agouti-related protein (AGRP) is a naturally occurring antagonist of melanocortin action. It is expressed mainly in the arcuate nucleus where it plays an important role in the hypothalamic control of feeding and energy homeostasis by antagonism of central melanocortin 4 receptors in mammals. Besides in the brain, the melanocortin 4 receptor is expressed in numerous peripheral tissues in the chicken. To examine whether or not the peripheral melanocortin 4 receptor signaling could be regulated by AGRP, we cloned and localized the expression of the AGRP gene in the chicken. The chicken AGRP gene was found to encode a 154 or 165 amino acid protein, depending on the usage of two alternative translation initiation sites. The coding sequence consisted of three exons, like that of mammalian species. The C-terminal cysteine-rich region of the predicted AGRP displayed high levels of identity to mammalian counterparts (78-84%) and all 10 cysteine residues conferring functional conformation of AGRP were conserved; however, other regions showed apparently no homology, suggesting that biological activities of AGRP are located in its C-terminal region. RT-PCR analysis detected the AGRP mRNA in all tissues examined: the brain, adrenal gland, heart, liver, spleen, gonads, kidney, uropygial gland, skeletal muscle and adipose tissues. Interestingly, the skin also expressed the AGRP mRNA, where Agouti, another melanocortin receptor antagonist regulating hair pigmentation, is expressed in rodents. Most of those AGRP-expressing tissues have been demonstrated to express melanocortin 4 receptors and/or other subtypes of melanocortin receptor whose mammalian counterparts can bind AGRP. These results imply the possibility that some peripheral melanocortin systems could be regulated by the functional interaction between melanocortins and AGRP at melanocortin receptors in the chicken. (C) 2000 Elsevier Science B.V. All rights reserved.

    DOI: 10.1016/S0167-4889(00)00022-7

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  • A possible mechanism for feedback regulation of the mouse tyrosinase gene by its 3 ' non-coding RNA fragments

    S Takeuchi, T Takeuchi, H Yamamoto

    PIGMENT CELL RESEARCH   13 ( 2 )   109 - 115   2000年4月

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    記述言語:英語   出版者・発行元:MUNKSGAARD INT PUBL LTD  

    The 5' upstream regulatory region of the mouse tyrosinase gene contains a long (GA)n sequence, that may be capable of adopting a triple-helical conformation (triplex), We analyzed protein-DNA interactions in a part of the 5' upstream region containing the (GA)n sequence by gel retardation analysis and found evidence for a cell type-specific protein(s) that bound to this region. We also found a (TC)(10) sequence about 100 bp downstream from a polyadenylation site of the gene. Examination of tyrosinase cDNAs and Northern analysis indicated that this sequence is transcribed and removed during 3' end-processing of the mRNA, Based on the hypothesis that the (TC)(10) sequence binds to the (GA)n sequence and forms an intermolecular tripler, we performed the same gel retardation assay in the presence of the 3' non-coding RNA fragments containing the (UC)(10) sequence. The probe DNA failed to interact,vith the cell type-specific protein(s), These results suggest a novel hypothesis for the regulation of the mouse tyrosinase gene, i.e. that the 3' non-coding RNA fragments of mouse tyrosinase transcripts suppress its own expression at the transcriptional level. This might occur by preventing cell type-specific protein factor(s) from binding to the regulatory cis-elements in the 5' upstream region of the gene, possibly through a tripler formation, although this hypothesis remains to be proven.

    DOI: 10.1034/j.1600-0749.2000.130209.x

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  • Identification of epidermal growth factor mRNA-expressing cells in the mouse anterior pituitary

    J Honda, S Oomizu, Y Kiuchi, N Komatsu, S Takeuchi, S Takahashi

    NEUROENDOCRINOLOGY   71 ( 3 )   155 - 162   2000年3月

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    記述言語:英語   出版者・発行元:KARGER  

    Epidermal growth factor (EGF) produced within the pituitary gland is associated with the growth of pituitary cells in rats. The aim of the present study was to localize EGF- and EGF receptor-expressing cells, and to clarify the involvement of EGF in DNA replication in 2-month-old male mouse pituitary cells, In situ hybridization of the pituitaries of these mice demonstrated that EGF mRNA was expressed in the anterior and intermediate lobes. Within the anterior pituitary, EGF mRNA-expressing cells were medium-sized and round, and made up 40% of the total number of secretory cells. EGF receptor mRNA was only detected in anterior pituitary cells. Forty-seven percent anterior pituitary cells expressed EGF receptor mRNA, An immunocytochemical study showed that most somatotropes and some mammotropes expressed EGF mRNA, When anterior pituitary cells were enzymatically dissociated and cultured in serum-free medium, RT-PCR demonstrated both EGF mRNA and EGF receptor mRNA expression. Treatment with EGF (1 and 10 ng/ml) for 5 days stimulated DNA replication in mammotropes and corticotropes, These results indicate that the DNA replication in mammotropes and corticotropes is regulated by the paracrine and/or autocrine activity of EGF produced at least in part by these cell types themselves. Copyright (C) 2000 S. Karger AG, Basel.

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  • Epidermal growth factor, insulin, and estrogen stimulate development of prolactin-secreting cells in cultures of GH3 cells

    T Kakeya, S Takeuchi, S Takahashi

    CELL AND TISSUE RESEARCH   299 ( 2 )   237 - 243   2000年2月

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    記述言語:英語   出版者・発行元:SPRINGER VERLAG  

    Pituitary tumor GH3 cells synthesize and secrete both growth hormone (GH) and prolactin (PRL). Morphological and functional changes of GH3 cells induced by epidermal growth factor (EGF, 10 nM), insulin (300 nM), and estradiol-17 beta (E2, 1 nM) were studied. Treatment of cultures of GH3 cells for 6 days with EGF, insulin, or E2 alone, and with EGF plus E2 did not affect the total number of GH3 cells, but a combination of EGF, insulin, and E2 decreased the total number of GH3 cells compared with control treatment. DNA-synthesizing cells were detected by monitoring 5-bromo-2'-deoxyuridine (BrdU) uptake. EGF, E2, or a combination of EGF, insulin, and E2 significantly decreased the proportion of BrdU-labeled cells (21.1+/-1.7%, 21.0+/-1.4%, 18.2+/-1.3%; P<0.05, P<0.05, P<0.01, respectively) compared with control treatment (28.6+/-1.5%), but insulin did not (31.4+/-2.4%). Immunocytochemical analysis of GH3 cells cultured in 5% fetal calf serum-supplemented medium (control) showed that about 70% of all GH3 cells were GH-immunoreactive cells (GH-ir cells), apparently containing only GH, and 14% were mammosomatotrophs (MS cells), containing both GH and PRL, while PRL-immunoreactive cells (PRL-ir cells), containing only PRL, were not detected. No GH or PRL immunoreactivity could be detected in the remaining cells (15%). EGF decreased the proportion of GH-ir cells. The effects of EGF were enhanced by simultaneous exposure to insulin and E2; this decreased the proportion of GH-ir cells to about 20% of the total GH3 cells and significantly increased the proportion of MS cells to 300% of controls. Treatment with EGF plus insulin, EGF plus E2, or a combination of EGF, insulin, and E2 all stimulated the appearance of PRL-ir cells. Exposure to EGF caused a significant decrease in GH mRNA (P<0.01) and a significant increase in PRL mRNA (P<0.05). These observations suggest that EGF is closely involved in differentiation of PRL-ir cells from GH-ir cells via MS cells in GH3 cell cultures. Cytosine arabinoside (10(-7) M), an inhibitor of cell division, did not affect the changes in proportion of the three cell types induced by treatment with a combination of EGF, insulin, and E2. It is therefore probable that the transdifferentiation does not require mitosis of the GH3 cells.

    DOI: 10.1007/s004410050021

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  • Immunocytochemical and immuno-electron-microscopical study ofsomatotrophs in ICR and non-obese diabetic(NOD)mice.

    Cells Tissues Organs   166   31 - 39   2000年

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  • Molecular cloning and characterization of the chicken pro-opiomelanocortin (POMC) gene

    S Takeuchi, K Teshigawara, S Takahashi

    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH   1450 ( 3 )   452 - 459   1999年7月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    The gene for pro-opiomelanocortin (POMC), a common precursor of melanocortins, lipotropins and beta-endorphin, was isolated in the chicken first among avian species. The chicken POMC gene was found to be a single copy gene and appeared to show the same structural organization as that of other species of different classes. The predicted POMC displayed the highest identity to Xenopus POMC(A) (60.1%), and consisted of 251 amino acid residues with nine proteolytic cleavage sites, suggesting that it could be processed to give rise to all members of the melanocortin family, including adrenocorticotropic hormone and alpha-, beta- and gamma-melanocyte-stimulating hormones, as well as the other POMC-derived peptides. RT-PCR analysis detected the POMC mRNA in the brain, adrenal gland, gonads, kidney, uropygial gland and adipose tissues, each of which has been demonstrated to express melanocortin receptors. These results suggest that melanocortins act in a paracrine and/or autocrine manner to control a variety of functions both in the brain and in the peripheral tissues in the chicken. (C) 1999 Elsevier Science B.V. All rights reserved.

    DOI: 10.1016/S0167-4889(99)00046-4

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  • A possible involvement of melanocortin 3 receptor in the regulation of adrenal gland function in the chicken

    S Takeuchi, S Takahashi

    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH   1448 ( 3 )   512 - 518   1999年1月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    The melanocortin 3 receptor (MC3-R) in the melanocortin receptor family has been identified as a neural receptor subtype mainly expressed in the brain in mammals. We report here the isolation of the chicken gene for MC3-R, CMC3, displaying different tissue distribution from mammalian counterparts. The CMC3 gene was found to be a single copy gene encoding a 325 amino acid protein, sharing 75.3-76.8% identity with mammalian counterparts. When assessed by RT-PCR, the CMC3 mRNA was not detected in the brain but was exclusively expressed in adrenal glands, where Agouti-related protein/Agouti-related transcript (AGRP/ART), a newly identified endogenous antagonist of MC3-R, is expressed in mammals, raising the possibility that the CMC3 plays a role in complicated regulation of the gland function by melanocortins and AGRP/ART in the chicken. Noteworthy, MC1-R gene was found to be a quite unique member of the chicken MC-R family with regard to GC content and codon usage. It may reflect as yet unidentified evolutionary pressure operating specifically on the gene. (C) 1999 Elsevier Science B.V. All rights reserved.

    DOI: 10.1016/S0167-4889(98)00165-7

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  • Melanocortin receptor genes in the chicken - Tissue distributions

    S Takeuchi, S Takahashi

    GENERAL AND COMPARATIVE ENDOCRINOLOGY   112 ( 2 )   220 - 231   1998年11月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS INC  

    Two receptor genes belonging to the melanocortin receptor (MC-R) family were isolated in the chicken, the CMC4 and CMC5, each of which is a chicken homologue of the mammalian MC4-R and MC5-R, respectively. The CMC4 encodes a 331 amino acid protein, sharing 86.4-88.1% identity with mammalian analogs, and the CMC5 encodes a 325 amino acid protein, which is 72.3-79.1% identical to mammalian counterparts. Both genes contain no intron in their coding regions and exist in the chicken genome as single copy genes. Reverse transcription-PCR analysis revealed that the CMC4 mRNA is expressed in a nide variety of peripheral tissues, including the adrenal, gonads, spleen, and adipose tissues, as well as in the brain, where mammalian counterparts are exclusively expressed in the brain, indicating that the regulation of MC4-R gene expression differs between mammals and chickens. The CMC5 mRNA, on the other hand, is expressed in the liver, gonads, adrenal, kidney brain, and adipose tissues as well as in the uropygial gland. These findings raise the possibility that melanocortins affect a variety of functions both in the brain and in the peripheral tissues of the chicken. (C) 1998 Academic Press.

    DOI: 10.1006/gcen.1998.7167

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  • Insulin-like growth factor-I and its receptor in mouse pituitary glands

    J Honda, S Takeuchi, H Fukamachi, S Takahashi

    ZOOLOGICAL SCIENCE   15 ( 4 )   573 - 579   1998年8月

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    記述言語:英語   出版者・発行元:ZOOLOGICAL SOC JAPAN  

    Insulin-like growth factor-I (IGF-I) is produced in the liver and other peripheral tissues in response to growth hormone (GH) stimuli. IGF-I regulates diverse physiological functions in an autocrine and/or paracrine manner. IGF-I and IGF-I receptor (type-I receptor) are expressed in human and rat pituitary glands. However, the cell types of IGF-I-expressing cells and target cells of IGF-I in the pituitary glands are not known. The present study was aimed to identify the cell types of IGF-I-expressing cells and of its type-I receptor-expressing cells in mouse pituitary glands. In the mouse pituitary glands, IGF-I mRNA and IGF-I receptor mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR). IGF-I-expressing cells and its receptor-expressing cells were detected by non-radioisotopic in situ hybridization using mouse IGF-I cDNA and IGF-I receptor cDNA probes, and their cell types were immunocytochemically determined using antibodies raised against pituitary hormones. We found that somatotrophs expressed both IGF-I and IGF-I receptors, and some of corticotrophs expressed IGF-I receptors. Co-localization of IGF-I and GH in the same cultured pituitary cells was observed by dual-labelling immunocytochemistry. The present study demonstrated that pituitary IGF-I produced in somatotrophs regulated functions of somatotrophs and corticotrophs in an autocrine and/or paracrine manner.

    DOI: 10.2108/zsj.15.573

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  • Stimulatory effect of insulin-like growth factor I on proliferation of mouse pituitary cells in serum-free culture

    S Oomizu, S Takeuchi, S Takahashi

    JOURNAL OF ENDOCRINOLOGY   157 ( 1 )   53 - 62   1998年4月

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    記述言語:英語   出版者・発行元:J ENDOCRINOLOGY LTD  

    IGF-I is synthesized in the human and rat anterior pituitary glands. The present study was designed to clarify the growth-promoting action of IGF-I on mouse pituitary cells in a primary serum-free culture system. Proliferation of pituitary cells was detected by monitoring the cellular uptake of bromodeoxyuridine (BrdU). BrdU labelling in the nucleus was found in all types of secretory cells: corticotrophs, thyrotrophs, gonadotrophs (LH cells and FSH cells), somatotrophs and mammotrophs. IGF-I (75 ng/ml) stimulated the proliferation of corticotrophs and mammotrophs among the pituitary secretory cells. IGF-I receptor mRNA was detected in the cultured pituitary cells using reverse transcription (RT)-PCR, indicating that mouse pituitary cells expressed IGF-I receptors. Insulin (100 ng/ml) or IGF-I (7.5 ng/ml) failed to increase the percentage of BrdU-labelled cells. However, treatment with insulin (100 ng/ml) plus IGF-I (7.5 ng/ml) increased the percentage of BrdU-labelled cells in a synergistic-like manner. Genistein, a tyrosine kinase specific inhibitor, decreased the IGF-I-induced cell proliferation, indicating that IGF-I acts through IGF-I receptors. IGF-I mRNA was also detected in the cultured pituitary cells by RT-PCR, and its peptides were immunocytochemically detected. The present results demonstrate that all types of pituitary secretory cells have the ability to proliferate in our serum-free culture system. IGF-I synthesized in the pituitary gland may stimulate the growth of pituitary cells, in particular corticotrophs and mammotrophs, by an autocrine or paracrine mechanism.

    DOI: 10.1677/joe.0.1570053

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  • Augmentation of prolactin release by α-melanocyte stimulating hormone is possibly mediated by melanocortin 3-receptors in the mouse anterior pituitary

    Zoological Science   15 ( 4 )   567 - 572   1998年

  • Evolutionary conserved telomeric location of BBCI and MCIR on a microchromosome questions identity of MCIR and a pigmentation locus on chromosome 1 in chicken

    chromosome Research   6   651 - 654   1998年

  • Molecular cloning of the chicken melanocortin 2(ACTH)-receptor gene.

    Biochimica et Biophysica Acta   1403 ( 1 )   102 - 108   1998年

  • Expression of neural cell odnesion molecules in the mouse anterior pituitary gland and pitraitary tumor cells

    Biomedical Research   19 ( 4 )   269 - 277   1998年

  • メラノコルチン受容体

    生体の科学,医学書院   48 ( 5 )   426 - 429   1997年

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  • Insulin-like growth factor-I stimulates proliferation of mouse uterine epithelial cells in primary culture

    Proceedings of the Society for Experimental Biology and Medicine   215,412-417   1997年

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  • Insulin-like growth factor-Ⅰ system in the mouse pituitary

    Advances in Comparative Endocrinology   1123 - 1126   1997年

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  • A possible involvement of melanocortin 1-receptor in regulating feather color pigmentation in the chicken

    S Takeuchi, H Suzuki, M Yabuuchi, S Takahashi

    BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION   1308 ( 2 )   164 - 168   1996年8月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    The Extended black (E) locus on chromosome 1 acts within the melanocyte to regulate feather color pigmentation in the chicken. Several alleles exhibiting different pigmentation have been described and their phenotypes are similar to those of the murine extension locus which encodes melanocortin 1-receptor (MC1-R), the receptor for alpha-melanocyte-stimulating hormone (alpha-MSH). To investigate whether the MC1-R gene is responsible for E-locus function, we examined the structure of MC1-R in E-locus mutants by RFLP analysis and genomic DNA sequencing. In the most recessive allele (e(y)), which exhibits a uniformly red-yellow pigmentation, MC1-R was found to contain amino acid substitutions possibly causing functional deficiency. On the other hand, in the most dominant allele (E), which confers a uniformly black pigmentation, MC1-R possessed mutation responsible for a constitutively active MC1-R and resultant black coat color in mice. Our finding that the structure of MC1-R was affected by individual E-locus alleles strongly suggests that MC1-R is associated with the E-locus. Furthermore, since the same mutation of MC1-R was found in mice and chickens that exhibit the same pigmentation, it is possible that the regulatory mechanism of MC1-R function is shared in chickens and mammals.

    DOI: 10.1016/0167-4781(96)00100-5

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  • Molecular cloning and sequence analysis of the chick melanocortin 1-receptor gene

    S Takeuchi, H Suzuki, S Hirose, M Yabuuchi, C Sato, H Yamamoto, S Takahashi

    BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION   1306 ( 2-3 )   122 - 126   1996年5月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    The chick melanocortin 1-receptor gene was isolated. It is found to be an intronless gene encoding a 314 amino acid protein, sharing 64% identity with mammalian counterparts. A cis-element responsible for melanocyte-specific transcription is found in its 5' upstream region. It is probable that the expression of the receptor in melanocytes is closely correlated with that of melanogenesis-related genes.

    DOI: 10.1016/0167-4781(96)00026-7

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  • The Strain-dependent constitutive expression of murine serum amyloid-P component is regulated at the transcriptional level

    Biochimica et Biophysica Acta   1131(3),261-269   1992年

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  • Phylogeny of Regulatory Regions of Vertebrate Tyrosinase Genes

    Pigment Cell Research   5(5),284-294   1992年

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  • Structural changes and morphometric analysis of the pituitary gland after hemorrhage induced by intraperitoneal injection of hypertonic solution in mice.

    Biomedical Research   13(4),253-258   1992年

  • A morphometric study on pituitary pars intermedia cells of male mice fed a liquid diet supplemented with urea.

    Zoological Science   8,899-903   1991年

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  • Melanization in albino mice transformed by introducing cloned mouse tyrosinase gene.

    Development   108,223-227   1990年

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  • Melanin production in cultured albino melanocytes transfected with mouse tyrosinase cDNA.

    Japanease Journal of Genetics   64,121-135   1989年

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  • Expression of tyrosinase gene in amelanotic mutant mice.

    Biochemical and Biophysical Research Communication   155,470-475   1988年

  • Cloning and sequencing of mouse tyrosinase cDNA.

    Japanease Journal of Genetics   62,271-274   1987年

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共同研究・競争的資金等の研究

  • 下垂体ホルモンの下垂体外発現の生理学的意義と局所的ホルモン調節系の分子機構に関する研究

    2001年

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    資金種別:競争的資金

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  • メラノコルチン機能及びその受容体遺伝子に関する系統発生学的研究

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    資金種別:競争的資金

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  • Study on proliferation and differentiation of utenus and pituitary cells

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    資金種別:競争的資金

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  • Phylogenic Study on Melanocortin Function and their Receptor Genes

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    資金種別:競争的資金

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  • Phylogenic Study on MSH Function and Its Receptor Gene

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    資金種別:競争的資金

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  • 子宮及び下垂体細胞の増殖・分化に関する研究

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    資金種別:競争的資金

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