Expression of the 1,25-dihydroxyvitamin D3-24-hydroxylase gene in rat intestine: Response to calcium, vitamin D3 and calcitriol administration in vivo

Authors

  • Jacques Lemay,

    1. Centre de recherche clinique André-Viallet, Hǒpital Saint-Luc, Montréal, Canada
    2. Département de Pharmacologie, Faculté de médecine, Université de Montréal, Montréal, Canada
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  • Christian Demers,

    1. Centre de recherche clinique André-Viallet, Hǒpital Saint-Luc, Montréal, Canada
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  • Geoffrey N. Hendy,

    1. Departments of Medicine and Physiology and Royal Victoria Hospital, McGill University, Montréal, Canada
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  • Edgard E. Delvin,

    1. Departement de Biochimie, Faculte de médecine, Université de Montréal, Canada
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  • Marielle Gascon-Barré

    Corresponding author
    1. Centre de recherche clinique André-Viallet, Hǒpital Saint-Luc, Montréal, Canada
    2. Département de Pharmacologie, Faculté de médecine, Université de Montréal, Montréal, Canada
    • Centre de recherche clinique André-Viallet Hǒpital Saint-Luc 264 René-Lévesque Blvd. East Montréal (Québec), H2X 1P1, Canada
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Abstract

The 25(OH)D3/1,25(OH)2D3 24-hydroxylase (24-hydroxylase) displays an induction profile responsive to vitamin D (D) abundance and is hence only observed in normal extracellular Ca2+ concentrations. However, the participation of Ca2+ in the expression of the 24-hydroxylase gene in vivo is not known. The present studies investigate the role played by the circulating Ca2+ and the D3 and/or 1,25(OH)2D3 status on the 1,25(OH)2D3-mediated inducibility of the 24-hydroxylase gene in rat duodenum. Hypocalcemic D-depleted rats were supplemented with calcium alone to normalize serum Ca2+ without normalizing the D3 status or were acutely or chronically supplemented with D3 or 1,25(OH)2D3. Messenger RNA for the 24-hydroxylase was undetectable in the intestine of hypocalcemic D-depleted rats, and short- or long-term calcium supplementation was completely unsuccessful in inducing its expression. By contrast, acute 1,25(OH)2D3 administration led to significant increases in the levels of expression of the gene which was independent of the calcium intake, the prevailing circulating Ca2+, and the D3 or 1,25(OH)2D3 status. Moreover, 24-hydroxylase gene expression was only found to respond to acutely administered 1,25(OH)2D3, the mRNA levels being unaltered following continuous exposure to physiological or pharmacological doses of the hormone for 7 days. Time-course studies revealed, however, that induction of the gene was clearly apparent early in the 1,25(OH)2D3 supplementation course but gradually faded by 3 days to return to basal uninduced levels by 7 days, suggesting the presence of intestinal adaptation mechanism(s) which down-regulated the responsiveness in the continuous presence of 1,25(OH)2D3. Our data show the lack of effect of calcium alone or in combination with 1,25(OH)2D3 on the in vivo induction of the 24-hydroxylase gene expression in rat intestine. By rapidly reacting to surges in 1,25(OH)2D3 concentrations, the 24-hydroxylase efficiently controls the amount of 1,25(OH)2D3 in intestine as the first step in the biotransformation pathway aimed at the irreversible clearance of the secosteroid hormone. (J Bone Miner Res 1995;10:1148–1157)

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