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Cloning of homeobox genes involved in the differentiation of placental cells producing peptide hormones

Research Project

Project/Area Number 04454559
Research Category

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

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionNagoya University

Principal Investigator

SEO Hisao  Nagoya Univ., Res.Inst.Environ. Med.Professor, 環境医学研究所, 教授 (40135380)

Co-Investigator(Kenkyū-buntansha) MIYAMOTO Norihiro  Nagoya Univ., Res.Inst.Environ. Med.Research Associate, 環境医学研究所, 助手 (10221615)
MURATA Yoshiharu  Nagoya Univ., Res.Inst.Environ. Med.Associate Professor, 環境医学研究所, 助教授 (80174308)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1994: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1993: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1992: ¥4,100,000 (Direct Cost: ¥4,100,000)
KeywordsPax-8 / placenta / thyroglobulin / redox / ルシフェラーゼ / TTF-1 / TBG / HNF-1 / POU-domain protein / ホメオボックス / 0ct-1 / Pit-1
Research Abstract

Placental villi synthesize hormones such as plaental lactogen (PL) and chorionic gonadotropin (CG). These peptide hormones play important role for the maintenace of pregnacy and the development and growth of fetus. It is well known that the genes for placental lactogen and pituitary grwoth hormone (GH) share sequence homology and originate from a common ancestral gene. Also chorionic gonadotropin and pituitary gonadotropins (luteinizing hormone=LH and follicle stimulating hormone=FSH) and thyroid stimulating hormone (TSH) originate from a common ancestral gene. Recently, it has been shown that tissue specific expression of GH and TSH is controlled by a transcriptional factor, Pit-1, belonging to POU family protein. This finding lead us to postulate that POU family transcription factor (s) may play important role for the expression of placental hormones. It was thsu investigated whether placental tissue expresses transcription factor belonging to POU family. To study whether Pit-1 is ex … More pressed in human placental tissue or not, a cDNA coding for human Pit-1 was cloned by reverse transcription-polymerase chain reaction (RT-PCR) using pituitary RNA as a template. Using this cDNA,it was revealed that placental tissue does not express Pit-1 gene, suggesting other transcription factor is involved in the placental tissue expression of PL and CG.The search for the expression of POU family by RT-PCR revealed that Oct-1 is expressed in placenta. The result indicated that Pit-1 like transcription factor might be present in placenta since Oct-1 heterodimerizes with Pit-1 and augments its action.
Search for other transciption factors revealed that Pax-8, belonging to paired domain protein is also expressed in the placenta. We have demonstrated that Pax-8 play important role for the thyroid specific expression of thyroglobulin gene. The results indicate the possible involvement of Pax-8 for the placental specific expression of peptide hormones. Recently it was demonstrated that post-translational modification such as phosphorylation and reduction is required for the activation of transcription factors. For example, Pit-1 is activated by phosphorylation. However, it has never been studied whether post-translational midification is also required for the activation of Pax-8. Our study revealed that Pax-8 is activated by reduction but not by phosphorylation. It is thus speculated that redox regulation is important for the tissue specific expression of placental genes. Less

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (56 results)

All Other

All Publications (56 results)

  • [Publications] 宮崎 高志: "妊娠経過中のヒト胎盤遺伝子発現の変化" 名古屋大学環境医学研究所年報. 46. 印刷中 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 神部 福司: "Paired domain遺伝子に属するPax-8mRNAのラット胎盤における検出" 名古屋大学環境医学研究所年報. 45. 159-160 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 神部 福司: "培養甲状腺株(FRTL-5細胞)における血清、TSHおよびインスリン刺激によるサイログロブリン(TG)プロモーター活性とTGmRNAの変動21GC02:名古屋大学環境医学研究所年報" 45. 156-158 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] S.Tsukahara: "Increse in Pit-1 mRNA is not required for the estrogen-induced expression of prolactin geneand lactotroph proliferation." Endocrine Journal. 41. 579-584 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 神部 福司: "ヒト血中甲状腺ホルモン輸送蛋白TBGのcDNAのクローニングおよびゲノム遺伝子のクローニング" 日本臨床. 52. 875-879 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] N.Tsukamoto: "Octreotide treatment results in the inhibition of GH gene expression in the adenoma of the patients with acromegaly." Endocrine Joumal. 41. 437-444 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Tsukahara S,Kambe F,Katoh T,Suganuma N,Tomoda Y,Seo H.: "Cloning of the human Pit-1 POU-box." Environmental Medicine. 36. 55-58 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shibata H,Suganuma N,Yamamoto N,Murata Y,Kondo I,Nakamura K,Tomoda Y,Matsui N,Seo H.: "Gonadotropin induces expression of c-fos and c-jun genes in rat ovaries." Endocrinologia Japonica. 39. 455-460 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ohwaki M,Suganuma N,Seo H,Nawa A,Kikkawa F,Narita O,Matsui N,Tomoda Y.: "Source of prolactin in human follicular fluid." Endocrinologia Japonica. 39. 601-607 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kambe F,Seo H,Mori Y,Murata Y,Janssen OE,Refetoff S,Matsui N.: "An additional carbohydrate chain in the variant thyroxinebinding globulin-Gary (TBG^<Asn-96>) inpairs its secretion." Molecular Endocrinoogy. 6. 443-449 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Lee J,Murata Y,Seo H,Menjo M,Torii S,Matsui N.: "The effect of thyroid hormone on fibronectin messenger ribonucleic acid levels in primary cultured rat hepatocytes." Endocrinology. 130. 2733-2738 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Miyamoto N,Seo H,Kanda K,Hidaka H,Matsui N.: "A 3', 5'-cyclic adenosinemonoPhosphate-dependent pathway is responsible for a rapid increase in c-fos messenger ribonucleic acid by adrenocorticotropin." Endocrinology. 130. 3231-3236 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ohno M,Seo H,Imai T,Murata Y,Miyamoto N,Satoh Y,Funahashi H,Takagi H,Matsui N.: "ACTH increases expression of c-fos, c-jun and beta-actin genes in the dexamethasone treated rat adrenals." Endocrinologia Japonica. 39. 377-383 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kambe F,Tsukahara S,Kato T,Seo H.: "The POU-domain protein Oct-1 is widely expressed in adult rat organs." Biochimica et Biphysica Acta. 1171. 307-310 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Suganuma N,Kikkawa F,Seo H,Matsui N,Tomoda Y.: "Poly (adenosine diphosphate-ribose) synthesis in the anterior pituitary of the female rat throughout the estrous cycle : Study of possible relation to cell proliferation and prolactin gene expression." Journal of Endocrinological Investigation. 16. 475-480 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hayash Y,Janssen O,Weiss R,Murata Y,Seo H,Samuel Refetoff: "The relative expression of mutant and normal thyroid hormone receptor genes in patients with generalized resistance to thyroi hormone determined by estimation of their specific messenger ribonucleic acid products." Journal of Clinical Endocrinology and Metabolism. 76. 64-69 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Fujieda M,Murata Y,Hayashi H,Kambe F,Matsui N,Seo H.: "Effect ofthyroid hormone on epidermal growth factor gene expression in mouse submandibular gland." Endocrinology. 132. 121-125 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Menjo M,Murata Y,Fuiji T,Murata Y,Seo H.: "Effects of thyroid and glucocorticoid hormones on the level of messenger ribonucleic acid for iodo-thyronine thpe I 5'-deiodinase in rat primary hepatocyte cultures grown asspheroids." Endocrinology. 133. 2984-2990 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Miura Y,Mori Y,Yamamori I,Tani Y,Murata Y,Yoshimoto M.Kinoshita E,Matsumoto T,Oiso Y,Seo H.: "Sequence of a variant thyroxine-binding globulin (TBG) in a family with partial TBG deficiency in Japanese (TBG-PDJ)." Endocrine Journal. 40. 127-132 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hayashi Y,Mori Y,Janssen O,Sunthornthepvarakul T,Weiss R,Takeda K,Weinberg M,Seo H,Bell GI,Refetoff S.: "Human thyroxinebinding globulin gene : Complete sequence and transcriptional regulation." Molecular Endocrinology. 7. 1049-1060 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Tsukahara S,Kambe F,Suganuma N,Tomoda Y,Seo H.: "Increase in Pit-1 mRNA is not required for the estrogen-induced expression of prolactin gene and lactotroph proliferation." Endocrine Journal. 41. 579-584 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Tsukamoto N,Nagaya T,Kuwayama A,Takano K,Shizume K,Sugita K,Seo H.: "Octreotide treatment results in the inhibition of GH gene expression in the adenoma of the patients with acrogmegaly." Endocrine Journal. 41. 437-444 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Matsuyama Morita T,Imai T,Murata Y,Kambe F,Funahashi H,Takagi H,Seo H.: "Adrenocorticotropic hormone (ACTH) increases the expression of its own receptor gene." Endocrine Journal. (in press.). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Tsukahara S.: "Cloning of the human Pit-1 POU-box." Environmental Medicine. 36. 55-58 (1992)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shibata H.: "Gonadotropin induces expression of c-fos and c-jun genes in rat ovaries." Endocrinologia Japonica. 39. 455-460 (1992)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ohwaki M.: "Source of prolactin in human follicular fluid." Endocrinologia Japonica. 39. 601-607 (1992)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kambe F.: "An additional carbohydrate chain in the variant thyroxine-binding globulin-Gary (TBG^<Asn-96>)inpairs its secretion." Molecular Endocrinoogy. 6. 443-449 (1992)

    • Related Report
      1994 Annual Research Report
  • [Publications] Lee J.: "The effect of thyroid hormone on fibronectin messenger ribonucleic acid levels in primary cultured rat hepatocytes." Endocrinology. 130. 2733-2738 (1992)

    • Related Report
      1994 Annual Research Report
  • [Publications] Miyamoto N.: "A3′,5′-cyclic adenosine monophosphate-dependent pathway is responsible for a tapid increase in c-fos messenger ribonucleic acid by adrenocorticotropin." Endocrinology. 130. 3231-3236 (1992)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ohno M.: "ACTH increases expression of c-fos,c-jun and β-actin genes in the dexamethasone treated rat adrenals." Endocrinologia Japonica. 39. 377-383 (1992)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kambe F.: "The POU-domain protein Oct-1 is widely expressed in adult rat organs." Biochimica et Biphysica Acta. 1171. 307-310 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] 神部福司: "RT-PCR法を用いた新しいPOU遺伝子のクローニングの試み." 名古屋大学環境医学研究所年報. 44. 154-157 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Suganuma N.: "Poly-ADP)synthesis in the anterior potuitary of the female rat throughout the extrous cycle:Study of possible relation to cell proliferation and prolactin gene expression." Journal of Endocrinological Investigation. 16. 475-480 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hayashi Y.: "The relative expression of mutant and nomal thyroidhormone receptor genes in patients with generalizedresistance to thyroid hormone determinedby estimation of their specific mRNA products." Journal of Clinical Endocrinology and Metabolism. 76. 64-69 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Fujieda M.: "Effect of thyroid hormone on epidermal.growth Factor gene expression in mouse submandibular gland." Endocrinology. 132. 121-125 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Menjo M.: "Effects of thyroid and glucocorticoid hormones on the level of messenger ribonucleic acid for iodo-thyronine thpe I 5′-deiodinase in rat primary hepatocyte cultures grown as spheroids." Endocrinology. 133. 2984-2990 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Miura Y.: "Sequence of a variant thyroxine-binding globulin(TBG)in a family with partial TBG deficiency in Japanese(TBG-PDJ)." Endocrine Journal. 40. 127-132 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] 妹尾久雄: "成長ホルモン遺伝子群の発現調節-組織特異的発現調節を中心に-" 医学のあゆみ. 165. 247-251 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hayashi Y.: "Human thyroxine-binding globulin gene:Complete sequence and transcriptional regulation." Molecular Endocrinology. 7. 1049-1060 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] 神部福司: "トランスフェクションを用いたTBG異常症発症機序の研究." Modern Physician. 13. 939-944 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] 神部福司: "Paired domain遺伝子に属するPax-8mRNAのラット胎盤における検出" 名古屋大学環境医学研究所年報. 45. 159-160 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 神部福司: "ヒト血中甲状腺ホルモン輸送蛋白TBGのcDNAおよびゲノム遺伝子のクローニング." 日本臨床. 52. 875-879 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Tsukahara S.: "Increase in Pit-1 mRNA is not required for the estrogen-induced expression of prolactin gene and lactotroph proliferation." Endocrine Journal. 41. 579-584 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Tsukamoto N.: "Octreotide treatment results in the inhibition of GH gene expression in the adenoma of the patients with acrogmegaly." Endocrine Journal. 41. 437-444 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hayamizu S.: "Glucocorticoids potentiate the action of atrial natriuretic polypeptide in adrenalectomized rats." Endocrinology.135. 2459-2464 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Miura Y.: "A truncated TBG due to a frameshift mutation is retained within the rough endoplasmic reticulum:A possible mechanism of complete TBG deficiency in Japanese." Journal of Clinical Endocrinology and Metabolism. 78. 283-287 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Miura Y.: "Impaired intracellular transport contributes to partial thyroxine-binding globulin deficiency in a Japanese Family." Journal of Clinical Endocrinology and Metabolism. 79. 740-744 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Matsuyama Morita T.: "Adrenocorticotropic hormone(ACTH)increases the expression of its own receptor gene." Endocrine Journal. (in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 宮崎高志: "妊娠経過中のヒト胎盤遺伝子発現の変化." 名古屋大学環境医学研究所年報. 45(印刷中). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 神部福司: "転写調節因子TTF-1,Pax-8はサイログロブリン遺伝子プロモーターに結合する." 名古屋大学環境医学研究所年報. 45(印刷中). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] S.Tsukahara: "Increase in Pit-1 mRNA is not required for the induction of the PRL gene expression by estrogen." Environmental Medicine. 37. 35-38 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Y.Hayashi: "Human thyroxine-binding globulin gene:complete sequence and transcriptional regulation." Molecular Endocrinology. 7. 1049-1060 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 神部 福司: "Paired domain遺伝子に関するPax-8 mRNAのラット胎盤における検出" 環境医学研究所年報. 45. (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 神部 福司: "培養甲状腺細胞株(FRTL-5細胞)における血清,TSHおよびインスリン刺激によるサイログロブリン(TG)プロモーター活性とTG mRNAの変動" 環境医学研究所年報. 45. (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] F.Kambe: "The POU-domain protein Oct-1 is widely expressed in adult rat organs." Biochimica et Biophysica Acta. 1171. 307-310 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] S.Tsukahara: "Cloning of the human Pit-1 POU-box." Environmental Medicine. 36. 55-58 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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