Regular Article
Regulation of 25-Hydroxyvitamin D3 1α-Hydroxylase Gene Expression by Parathyroid Hormone and 1,25-Dihydroxyvitamin D3

https://doi.org/10.1006/abbi.2000.1970Get rights and content

Abstract

The conversion of 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) takes place mainly in the kidney and is catalyzed by the enzyme 1α-hydroxylase. Parathyroid hormone (PTH) and 1,25-(OH)2D3 are well-known regulators of this tightly controlled step, but the mechanisms by which they modulate 1α-hydroxylase activity have not been fully delineated. Northern analysis showed PTH and forskolin rapidly and transiently increase 1α-hydroxylase expression in AOK-B50 cells and HKC-8 cells. Actinomycin D treatment blocks the increase, but cycloheximide does not. No decrease of 1α-hydroxylase transcript by 1,25-(OH)2D3 was observed in either cell line, although 24-hydroxylase levels were strongly induced by 1,25-(OH)2D3 treatment. 1,25-(OH)2D3 suppressed the 1α-hydroxylase transcript in vivo both in the presence and absence of exogenously supplied PTH. These results suggest that the stimulatory action of PTH is directly on the 1α-hydroxylase gene, while the repressive action of 1,25-(OH)2D3 does not involve the parathyroid gland but is nevertheless indirect.

References (47)

  • L.C. Racusen et al.

    J. Lab. Clin. Med.

    (1997)
  • M.J. Ryan et al.

    Kidney Int.

    (1994)
  • T. Suda et al.

    J. Nutr.

    (1970)
  • P. Chomczynski et al.

    Anal. Biochem.

    (1987)
  • T. Monkawa et al.

    Biochem. Biophys. Res. Commun.

    (1997)
  • A. Murayama et al.

    Biochem. Biophys. Res. Commun.

    (1998)
  • C. Zierold et al.

    J. Biol. Chem.

    (1995)
  • K.S. Chen et al.

    Biochim. Biophys. Acta

    (1995)
  • J. Hilpert et al.

    J. Biol. Chem.

    (1999)
  • H.L. Henry

    Biochem. Biophys. Res. Commun.

    (1977)
  • H.M. Darwish et al.

    Arch. Biochem. Biophys.

    (1996)
  • R. Zhang et al.

    J. Biol. Chem.

    (1997)
  • H.F. DeLuca

    Biochem. Soc. Trans.

    (1982)
  • H.L. Henry

    J. Cell. Biochem.

    (1992)
  • G.K. Fu et al.

    Mol. Endocrinol.

    (1997)
  • D. Fraser et al.

    N. Engl. J. Med.

    (1973)
  • C.R. Scriver et al.

    N. Engl. J. Med.

    (1978)
  • M. Garabedian et al.

    Proc. Natl. Acad. Sci. U.S.A.

    (1972)
  • Y. Tanaka et al.

    Science

    (1974)
  • A. Murayama et al.

    Endocrinology

    (1999)
  • H.L. Brenza et al.

    Proc. Natl. Acad. Sci. USA

    (1998)
  • X.F. Kong et al.

    Proc. Natl. Acad. Sci. U.S.A.

    (1999)
  • J. Russell et al.

    Endocrinology

    (1986)
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    To whom correspondence should be addressed at the Department of Biochemistry, University of Wisconsin—Madison, 433 Babcock Drive, Madison, WI 53706-1544. Fax: (608) 262-7122. E-mail: [email protected].

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