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Elucidetion of pathogeness of derangements in Calcinm metabolism

Research Project

Project/Area Number 13671149
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionThe University of Tokyo

Principal Investigator

FUKUMOTO Seiji  The University of Tokyo, Department of Medicine, Lecturer, 医学部附属病院, 講師 (30202287)

Co-Investigator(Kenkyū-buntansha) TAKEUCHI Yasuhiro  The University of Tokyo, Department of Medicine, Research Associate, 医学部附属病院, 助手 (50202164)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordscalcium-sensing receptor / Hypocalcemia / Hypercalcemia / mutation
Research Abstract

Calcium-sensing receptor (CaSR) is a member of G protein-coupled receptors that has been identified as a essential molecular for regulating secretion of parathyroid hormone (PTH). Extracellular Ca inhibits secretion of PTH through CaSR and there is a strict negative feedback system between serum Ca and PTH secretion. It has been already known that heterozygous inactivating mutations of CaSR result in familial hypocalciuric hypercalcemia (FHH) characterized by relative hypocalciuria and mild hypercalcemia, whereas heterozygous activating mutations of CaSR cause autosomal dominant hypocalcemia (ADH) with relative hypercalciuria and PTH-deficient hypocalcemia. However, the histology of parathyroid glands in patients with FHH has not been reported although clinical features of FHH are similar to those of patients with primary hyperparathyroidism, which is the typical cause of hypercalcemia. In addition, detailed clinical features of patients with AMD have been unknown, either. By examining mutations in CaSR gene and analyzing functional properties of mutant CaSRs in vitro, we have demonstrated that parathyroid glands in patients with FHH show distinct histological features called lipohyperplasia, which are different from those of patients with primary hyperparathyroidism. In addition, we have shown that some activating mutations of CaSR with severe activation cause Bartter-like syndrome by inhibiting renal outer medullary potassium channel in thick ascending limb of Henle. These results indicate the variability of clinical manifestations caused by mutations in CaSR gene and seem to have contributed to the establishment of the new classification of derangements in calcium metabolism based on molecular mechanisms.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Fukumoto S et al.: "Inactivating mutations of calcium-sensing receptor result in parathyroid lipohyperplasia"Diagn Mol Pathol. 10. 242-247 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fukumoto S et al.: "Fibroblast growth factor (FGF)-23 and hypophosphatemic rickets/osteomalacia"Endocr J. 48. 603-610 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Uchida M et al.: "Parathyroid hormone increases expression level of matrix metalloproteinase-13 in vivo"J Bone Miner Metab. 19. 207-212 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Watanabe S et al.: "Association between activating mutations of calcium-sensing receptor and Bartter's syndrome"Lancet. 360. 692-694 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagase T et al.: "A family of autosomal dominant hypocalcemia with positive correlation between serum calcium and magnesium : Identification of a novel gain-of function mutation (Ser820Phe) in the calcium-sensing receptor"J Clin Endocrinal Metab. 87. 2681-2687 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fukumoto S et al.: "Fibroblast growth facotr-23 is the phosphaturic factor in tumor-induced osteomalacia and may be phosphatonin"Curr Opin Nephrol Hypertens. 11. 385-389 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fukumoto S et al: "Inactivating mutations of calcium-sensing receptor result in parathyroid lipohyperplasia"Diagn Mol Pathol. 10(4). 242-247 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fukumoto S et al: "lipohyperplasiaFibroblast growth factor (FGF)-23 and hypophosphatemic rickets/osteomalacia"Endocr J. 48(6). 603-610 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Uchida M et al: "Parathyroid hormone increases expression level of matrix metalloproteinase-13 in vivo"J Bone Miner Metab. 19(4). 207-212 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Watanabe S et al: "Association between activating mutations of calcium-sensing receptor and Barrier's syndrome"Lancet. 360(9334). 692-694 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagase T et al: "A family of autosomal dominant hypocalcemia with positive correlation between serum calcium and magnesium : Identification of a novel gain-of-function mutation (Ser820Phe) in the calcium-sensing receptor"J Clin Endocrinol Metab. 87(6). 2681-2687 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fukumoto S et al: "Fibroblast growth facotr-23 is the phosphaturic factor in tumor-induced osteomalacia and may be phosphatonin"Curr Opin Nephrol Hypertens. 11(4). 385-389 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Watanabe S et al.: "Association between activating mutations of calcium-sensing receptor and Bartter's syndrome"Lancet. 360(9334). 692-694 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nagase T et al.: "A family of autosomal dominant hypocalcemia with a positive correlation between serum calcium and magnesium : Identification of a novel gain of function mutation (Ser820Phe) in the calcium-sensing receptor"J Clin Endocrinol Metab. 87(6). 2681-2687 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fukumoto S et al.: "Fibroblast growth facotr-23 is the phosphaturic factor in tumor-induced osteomalacia and may be phosphatonin"Curr Opin Nephrol Hypertens. 11(4). 385-389 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fukumoto S, et al.: "Inactivating mutations of calcium-sensing receptor result in parathyroid lipohyperplasia"Diagn Mol Pathol. 10(4). 242-247 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fukumoto S, et al.: "Fibroblast growth factor (FGF)-23 and hypophosphatemic rickets/osteomalacia"Endocr J. 48(6). 603-610 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Uchida M, et al.: "Inactivanting mutations of calcium-sensing receptor result in parathyroid lipohyperplasia"J Bone Miner Metab. 19(4). 207-212 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shimada T, et al.: "Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia"Proc Natl Acad Sci USA. 98(11). 6500-6505 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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