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Cloning of Transcriptional Regulatory Factors for the Prolactin Gene Using a TRH Knockout Mice.

Research Project

Project/Area Number 10470224
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionGunma University, School of Medicine

Principal Investigator

MORI Masatomo  FIRST DEPARTMENT OF INTERNAL MEDICINE, GUNMA UNIVERSITY SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (80174382)

Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥12,800,000 (Direct Cost: ¥12,800,000)
Fiscal Year 1999: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1998: ¥7,800,000 (Direct Cost: ¥7,800,000)
KeywordsTRH / Knockout mice / Hypothyroidism / Thyroid-stimulating hormone / Growth hormone / Luteinizing hormone / Follicule-stimulating hormone / Adrenocorticotropin / Prolactin
Research Abstract

We recently reported that TRH-deficient mice showed characteristic tertiary hypothyroidism. In the present study, we investigated how this tertiary hypothyroidism occurred particularly in pre- and postnatal stages. Immunohistochemical analysis revealed that a number of TSH-immunopositive cells in the TRH-/- pituitary on embryonic day 17.5 and at birth. The mutant pituitary at birth in pups born from TRH-deficient dams also showed no apparent morphological changes, indicating no requirement of either maternal or embryonic TRH for the development of pituitary thyrotrophs. In contrast, apparent decrease in number and level of staining of TSH-positive cells were observed after postnatal day 10 in mutant pituitary. Similar decreases were observed in the 8-week-old mutant pituitary, while no apparent changes were observed in other pituitary hormone-producing cells, and prolonged TRH administration completely reversed this effect. Consistent with these morphological results, TRH-/- mice showed normal thyroid hormone levels at birth, but the subsequent postnatal increase was depressed, resulting in hypothyroidism. As expected, TSH content in the TRH-/- pituitary showed a marked reduction to only 40% of that in the wild-type. Despite hypothyroidism in the mutant mice, both the pituitary TSH β and alpha mRNA levels were lower than those of the wild-type pituitary. These phenotypic changes were specific to the pituitary of thyrotrophs. These findings indicated that 1) TRH is essential only for the postnatal maintenance of the normal function of pituitary thyrotrophs, including the normal feedback regulation of the TSH gene by thyroid hormone ; 2) neither maternal nor embryonic TRH is required for normal development of the fetal pituitary thyrotrophs ; and 3) TRH-deficient mice do not exhibit hypothyroidism at birth. Moreover, reflecting its name, TRH has more critical effects on the pituitary thyrotrophs than on other pituitary hormone-producing cells.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (38 results)

All Other

All Publications (38 results)

  • [Publications] Shibusawa N.,Yamada M.,Hirato J.,Monden T.,Satoh T.,Mori M.: "Requirement of thyrptropin-releasing hormone (TRH) for the postnatal functions pituitary thyrotrophs : Ontogeny study of congenital tertiary hypothyoidism in mice"Molecular Endocrinology. 14. 137-146 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamada M.,Shibusawa N.,Hashida T.,Satoh T.,Mori M.: "Abundance of cyclo(His-Pro)-like immunoreactivity in the brain of TRH-deficient mice"Endocrinology. 140. 538-541 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Satoh T.,Monden T.,Ishizuka T.,Mitsuhashi T.,Yamada M.,Mori M.: "DNA binding and interaction with the nuclear receptor corepressor of thyroid hormone receptor are required for ligand-independent stimulation of the mouse preprothyrotropin-releasing hormone gene"Molecular Cell Endocrinology. 154. 137-149 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamada M.,Shibusawa N.,Hashida T.,Mori M.et al.: "Expression of thyrotropin-releasing hormone (TRH) receptor subtype 1 in mouse pancreatic islets and HIT-T15, an insulin-secreting clonal cell line"Life Science. 66. 1119-1125 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ohtani K.et al.: "Triglitazone (CS-045) inhibits beta-cell proliferation rate following stimulation of insulin secretion in HIT-T 15 cells"Endocrinology. 139. 178-172 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ren Y.et al.: "Stimulation of the preprothyrotropin-releasing hormone gene by epidermal growth factor"Endocrinology. 139. 195-203 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kamiya M.et al.: "Primary culture of cells from hyperfunctioning thyoid adenoma with an active mutation of Gsα"Moll Cell Endocrinol. 138. 137-142 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kashima K.et al.: "Effect of epalrestat, an aldose reductase inhibitor, on the gener action of oxygen-derived free radicals in neutrophils from streptozocin-induced diabetic rats"Endocrinology. 139. 3403-3408 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamada M.et al.: "Genomic organization and promoter function of the mouse uncoupling protein2 (UCP2) gene"FEBS Lett. 432. 65-69 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Satoh T.,Ishizuka T.,Monden T.,Shibusawa N.,Hashida T.,Kishi M.,Yamada M.,Mori M.: "Regulation of the mouse preprothyrotropin-releasing hormone gene by retonoic acid receptor"Endocrinology. 140. 5004-5013 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Monden T.,Kishi M.,Hosoya T.,Satoh T.,Wondisford FE.,Hollenberg AN.,Yamada M.,Mori M.: "p120 act as a specific coactivator for 9-cis-retinoic acid receptor (RXR) on peroxisome proliferator-activated receptor-gamma/RXR heterodimers"Molecular Endocrinology. 13. 1695-1703 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamada M.,Satoh T.,Monden T.,Mori M.: "Assignment of the thyrotropin-releasing hormone (TRH) gene to human chromosome 3q13.3-q21 by in situ hybridization"Cytogenetics and Cell Genetics. 87. 275 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamada M.,Konaka S.,Satoh T.,Monden T.,Mori M.: "Human thyrotropin-releasing hormone-associated peptide 3 (hTAP-3) in serum"Endocrine Journal. 46. 675-679 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamada M, Shibusawa N, Hashida T, Satoh T, Monden T, Prasad C, Mori M.: "Abundance of cyclo (His-Pro)-like immuno-reactivity in the brain of TRH-deficient mice."Endocrinology. 140. 538-541 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ohtani K, Shimizu H, Sato N, Mori M.: "Troglitazone (CS-045) inhibits beta-cell proliferation rate following stimulation of insulin secretion in HIT-T 15 cells."Endocrinology. 139. 172-178 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ren Y, Satoh T, Yamada M, Hashimoto K, Konaka S, Iwasaki T, Mori M.: "Stimulation of the preprothyrotropin-releasing hormone gene by epidermal growth factor."Endocrinology. 139. 195-203 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Murakami M, Kamiya Y, Yanagita Y, Koitabashi H, Nagamichi Y, Hosoi Y, Ogiwara T, Mizuma H, Iriuchijima T, Mori M.: "Primary culture of cells from hyperfunctioning thyroid adenoma with an activating mutation of G alpha S."Molecular and Cellular Endocrinology. 138. 137-142 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kashima K, Sato N, Sato K, Shimizu H, Mori M.: "Effect of epalrestat, an aldose reductase inhibitor, on the generation of oxygen-derived free radicals in neutrophils from streptozocin-induced diabetic rats."Endocrinology. 139. 3404-3408 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamada M, Hashida T, Shibusawa N, Iwasaki T, Murakami M, Monden T, Satoh T, Mori M.: "Genomic organization and promoter function of the mouse uncoupling protein 2 (UCP2) gene."FEBS Letter. 432. 65-59 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Satoh T, Monden T, Ishizuka T, Mitsuhashi T, Yamada M, Mori M.: "DNA binding and interaction with the nuclear receptor corepressor of thyroid hormone receptor are required for ligand-independent stimulation of the mouse preprothyrotropin-releasing hormone gene."Molecular and Cellular Endocrinology. 154. 137-149 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Satoh T, Ishizuka T, Monden T, Shibusawa N, Hashida T, Kishi M, Yamada M, Mori M.: "Regulation of the mouse preprothyrotropin-releasing hormone gene by retinoic acid receptor."Endocrinology. 140. 5004-5013 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Monden T, Kishi M, Hosoya T, Satoh T, Wondisford FE, Hollenberg AN, Yamada M, Mori M.: "p120 act as a specific coactivator for 9-cis-retinoic acid receptor (RXR) on peroxisome proliferator-activated receptor-gamma/RXR heterodimers."Molecular Endocrinology. 13. 1695-1703 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamada M, Konaka S, Satoh T, Monden T, Mori M.: "Human thyrotropin-releasing hormone-associated peptide 3 (hTAP-3) in serum."Endocrine Journal. 46. 675-679 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamada M, Satoh T, Monden T, Mori M.: "Assignment of the thyrotropin-releasing hormone (TRH) gene to human chromosome 3q13.3-q21 by in situ hybridization."Cytogenetics and Cell Genetics. 87. 275 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamada M, Shibusawa N, Hashida T, Ozawa A, Monden T, Satoh T, Mori M.: "Expression of thyrotropin-releasing hormone (TRH) receptor subtype 1 in mouse pancreatic islets and HIT-T15, an insulin-secreting clonal cell line."Life Science. 66. 119-1125 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shibusawa N, Yamada M, Hirato J, Monden T, Satoh T, Mori M.: "Requirement of thyrotropin-releasing hormone (TRH) for the postnatal functions of pituitary thyrotrophs : Ontogeny study of congenital tertiary hypothyroidism in mice."Molecular Endocrinology. 14. 137-146 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shibusawa N, Yamada M, Hirato J, Monden T, Satoh T, Mori M: "Requirement of thyrptropin-releasing hormone (TRH) for the postnatal functions of pituitary thyrotrophs: Ontogeny study of congenital tertiary hypothyroidism in mice"Molecular Endocrinology. 14. 137-146 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yamada M, Shibusawa N, Hashida T, Satoh T, Mori M: "Abundance of cyclo(His-Pro)-like immunoreactivity in the brain of TRH-deficient mice"Endocrinology. 140. 538-541 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Satoh T, Monden T, Ishizuka T, Mitsuhashi T, Yamada M, Mori M: "DNA binding and interaction with the nuclear receptor corepressor of thyroid hormone receptor are required for ligand-independent stimulation of the mouse preprothyrotropin-releasing hormone gene"Molecular Cell Endocrinology. 154. 137-149 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Satoh T, Ishizuka T, Monden T, Shibusawa N, Hashida T, Kishi M, Yamada M, Mori M: "Regulation of the mouse preprothyrotropin-releasing hormone gene by retinoic acid receptor"Endocrinology. 140. 5004-5013 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Monden T, Kishi M, Hosoya T, Satoh T, Wondisford FE, Hollenberg AN, Yamada M, Mori M: "p120 act as a specific coactivator for 9-cis-retinoic acid receptor (RXR) on peroxisome proloferator-activated receptor-gamma/RXR feterodimers"Molecular Endocrinology. 13. 1695-1703 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yamada M, Satoh T, Monden T, Mori M: "Assignment of the thyrotropin-releasing hormone (TRH) gene to human chromosome 3q13.3-q21 by in situ hybridization"Cytogenetics and Cell Genetics. 87. 275 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yamada M et al.: "Abundance of cyclo(His-Pro)-like immunoreactivity in the brain of TRH-deficient mouse." Endocrinology. 140. 538-541 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ohtani K et al.: "Triglitazone(CS-045)inhibits beta-cell proliferation rate following stimulation of insulin secretion in HIT-T 15 cells." Endocrinology. 139. 178-172 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ren Y et al.: "Stimulation of the preprothyrotropin-releasing hormone gene by epidermal growth factor." Endocrinology. 139. 195-203 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kamiya M et al.: "Primary culture of cells from hyper functioning thyroid adenoma with an active mutation of Gs α" Mol Cell Endocrinol. 138. 137-142 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kashima K et al.: "Effect of epalrestat,an aldose reductase inhibitor,on the generation of oxygenderived free radicals in neutrophils from streptozocin-induced diabetic rats." Endocrinology. 139. 3403-3408 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamada M et al.: "Genomic organization and promoter function of the mouse uncoupling protein 2(UCP2)gene." FEBS Lett. 432. 65-69 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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