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1995 Fiscal Year Final Research Report Summary

Role of vitamin D and parathyroid hormone on vitamin D metabolism in the kidney.

Research Project

Project/Area Number 06454527
Research Category

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

Allocation TypeSingle-year Grants
Research Field Functional basic dentistry
Research InstitutionShowa University

Principal Investigator

SHINKI Toshimasa  Showa University, School of Dentistry, Lecturer, 歯学部, 講師 (90138420)

Co-Investigator(Kenkyū-buntansha) KATAGIRI Takenobu  Showa University, School of Dentistry, Assistant, 歯学部, 助手 (80245802)
MIYAURA Chisato  Showa University, School of Dentistry, Lecturer, 歯学部, 講師 (20138382)
SUDA Tatsuo  Showa University, School of Dentistry, Professor, 歯学部, 教授 (90014034)
Project Period (FY) 1994 – 1995
Keywordsvitamin D / parathyroid hormone / vitamin D receptor / 1alpha-hydroxylase / 24-hydroxylase / kidney / mRNA / RT-PCR
Research Abstract

It is well established that vitamin D_3 is first metabolized in the liver to 25-hydroxyvitamin D_3 and then in the kidney to 1alpha, 25-dihydroxyvitamin D_3.1alpha, 25-Dihydroxyvitamin D_3 synthesized by 25-hydroxyvitamin D_3-1alpha-hydroxylase is biologically the most active metabolite of the vitamin D, and vitamin D receptors mediate its effects by controlling transcription of vitamin D-responsive genes. 24, 25-Dihydroxyvitamin D_3 synthesized by 25-hydroxyvitamin D_3-24-hydroxylase is thought to be an inactive metabolite. The vitamin D endocrine system is regulated reciprocally by renal 25-hydroxyvitamin D_3-1alpha-and 24-hydroxylases. Previously, we reported that renal proximal convoluted tubules, the major site of 1alpha, 25-dihydroxyvitamin D_3 production, have vitamin D receptors. In the presence of vitamin D receptors, renal proximal convoluted tubules cannot maintain the state of enhanced production of 1alpha, 25-dihydroxyvitamin D_3. To clarify this discrepancy, we proposed a … More working hypothesis for the reciprocal control of renal 25-hydroxyvitamin D_3-1alpha-and 24-hydroxylase activities. In the rat models of enhanced renal production of 1alpha, 25-dihydroxyvitamin D_3, expression of vitamin D receptors and 25-hydroxyvitamin D_3-24-hydroxylase mRNAs was strikingly suppressed in renal proximal convoluted tubules, but not in the cortical collecting ducts. In vitamin D deficient rats with up-regulated renal 25-hydroxyvitamin D_3-1alpha-hydroxylase activity, expression of vitamin D receptor mRNA in renal proximal convoluted tubules was also down-regulated, indicating that the down-regulation of vitamin D receptor mRNA is not the result of the enhanced production of 1alpha, 25-dihydroxyvitamin D_3. In Japanese quail models with up-regulated renal 25-hydroxyvitamin D_3-1alpha-hydroxylase activity by sex steroids, expression of vitamin D receptor mRNA was also down-regulated in the kidney, but not in the duodenum. These results suggest that the down-regulation of vitamin D receptors plays a critical role in the production of 1alpha, 25-dihydroxyvitaminD_3 in renal proximal convoluted tubules. Less

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Miyamoto Y.,et al.: "Regulation of vitamin D-responsive gene expression by fluorinated analogues of calcitriol in rat osteoblastic ROB-C26 cells." J.Biochem.118. 1068-1076 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iida K.,et al.: "Regulation of vitamin D receptors in regulating vitamin D activation in the kidney." Proc.Natl.Acad.Sci.USA. 92. 6112-6116 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohyama Y.,et al.: "Identification of a vitamin D-responsive element in the 5′-flanking region of the rat 25-hydroxyvitamin D_3 24-hydroxylase gene." J.Biol.Chem.269. 10545-10550 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishimura A.,et al.: "Regulation of messenger ribonucleic acid expression of 1α,25-dihydroxyvitamin D_3-24-hydroxylase in rat osteoblasts." J.Cell Biol.127. 1755-1766 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suda T.,et al.: "The mechanisms of regulation of vitamin D metabolism in the kidney." Current Opinion in Nephrology and Hypertension. 3. 59-64 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Imae Y.,et al.: "Biological activities of 24-fluoro-1α,25-dihydroxyvitamin D_2 and its 24-epimer." Biochem.Biophys.Acta.1213. 302-308 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyamoto, Y.et al.: "Regulation of vitamin D-responsive gene expression by fluorinated analogues of calcitriol in rat osteoblastic ROB-C26 cells." J.Biochem.118. 1068-1076 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iida, K.et al.: "Regulation of vitamin D receptors in regulating vitamin D activation in the kidney." Proc.Natl.Acad.Sci.USA. 92. 6112-6116 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohyama, Y.et al.: "Identification of vitamin D-responsive element in the 5'-flanking region of the rat 25-hydroxyvitamin D_3 24-hydroxylase gene." J.Biol.Chem.269. 10545-10550 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishimura, A.et al.: "Regulation of messenger ribonucleic acid expression of 1alpha, 25-dihydroxyvitamin D_3." J.Cell Biol.127. 1755-1766 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suda, T.et al.: "The mechanism of regulation of vitamin D metabolism in the kidney." Current Opinion in Nephrology and Hypertension. 3. 59-64 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Imae, Y.et al.: "Biological activities of 24-fuloro-1alpha, 25-dihydroxyvitamin D_2 and its 24-epimer." Biochem.Biophys Acta. 1213. 302-308 (1994)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1997-03-04  

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