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Expression of the 1,25‐dihydroxyvitamin D 3 ‐24‐hydroxylase gene in rat intestine: Response to calcium, vitamin D 3 and calcitriol administration in vivo
Author(s) -
Lemay Jacques,
Demers Christian,
Hendy Geoffrey N.,
Delvin Edgard E.,
GasconBarré Marielle
Publication year - 1995
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650100803
Subject(s) - medicine , endocrinology , calcitriol , gene expression , calcium , vitamin d and neurology , calcium metabolism , in vivo , cholecalciferol , trpv6 , extracellular , vitamin , basal (medicine) , biology , gene , biochemistry , microbiology and biotechnology , insulin
The 25(OH)D 3 /1,25(OH) 2 D 3 24‐hydroxylase (24‐hydroxylase) displays an induction profile responsive to vitamin D (D) abundance and is hence only observed in normal extracellular Ca 2+ concentrations. However, the participation of Ca 2+ in the expression of the 24‐hydroxylase gene in vivo is not known. The present studies investigate the role played by the circulating Ca 2+ and the D 3 and/or 1,25(OH) 2 D 3 status on the 1,25(OH) 2 D 3 ‐mediated inducibility of the 24‐hydroxylase gene in rat duodenum. Hypocalcemic D‐depleted rats were supplemented with calcium alone to normalize serum Ca 2+ without normalizing the D 3 status or were acutely or chronically supplemented with D 3 or 1,25(OH) 2 D 3 . 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) 2 D 3 administration led to significant increases in the levels of expression of the gene which was independent of the calcium intake, the prevailing circulating Ca 2+ , and the D 3 or 1,25(OH) 2 D 3 status. Moreover, 24‐hydroxylase gene expression was only found to respond to acutely administered 1,25(OH) 2 D 3 , 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) 2 D 3 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) 2 D 3 . Our data show the lack of effect of calcium alone or in combination with 1,25(OH) 2 D 3 on the in vivo induction of the 24‐hydroxylase gene expression in rat intestine. By rapidly reacting to surges in 1,25(OH) 2 D 3 concentrations, the 24‐hydroxylase efficiently controls the amount of 1,25(OH) 2 D 3 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)