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Age-related alteration of vitamin D metabolism in response to low-phosphate diet in rats

Published online by Cambridge University Press:  08 March 2007

Tsui-Shan Chau
Affiliation:
Central Laboratory of the Institute of Molecular Technology for Drug Discovery and Synthesis, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, PRC
Wan-Ping Lai
Affiliation:
Central Laboratory of the Institute of Molecular Technology for Drug Discovery and Synthesis, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, PRC
Pik-Yuen Cheung
Affiliation:
Central Laboratory of the Institute of Molecular Technology for Drug Discovery and Synthesis, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, PRC
Murray J. Favus
Affiliation:
Section of Endocrinology, Department of Medicine, The University of Chicago, Chicago, IL 60 637, USA
Man-Sau Wong
Affiliation:
Central Laboratory of the Institute of Molecular Technology for Drug Discovery and Synthesis, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, PRC
Corresponding
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Abstract

The responses of renal vitamin D metabolism to its major stimuli alter with age. Previous studies showed that the increase in circulating 1,25-dihydroxyvitamin D (1,25(OH)2D3) as well as renal 25-hydroxyvitamin D3 1-α hydroxylase (1-OHase) activity in response to dietary Ca or P restriction reduced with age in rats. We hypothesized that the mechanism involved in increasing circulating 1,25(OH)2D3 in response to mineral deficiency alters with age. In the present study, we tested the hypothesis by studying the expression of genes involved in renal vitamin D metabolism (renal 1-OHase, 25-hydroxyvitamin D 24-hydroxylase (24-OHase) and vitamin D receptor (VDR)) in young (1-month-old) and adult (6-month-old) rats in response to low-phosphate diet (LPD). As expected, serum 1,25(OH)2D3 increased in both young and adult rats upon LPD treatment and the increase was much higher in younger rats. In young rats, LPD treatment decreased renal 24-OHase (days 1–7, P<0·01) and increased renal 1-OHase mRNA expression (days 1–5, P<0·01). LPD treatment failed to increase renal 1-OHase but did suppress 24-OHase mRNA expression (P<0·01) within 7 d of LPD treatment in adult rats. Renal expression of VDR mRNA decreased with age (P<0·001) and was suppressed by LPD treatment in both age groups (P<0·05) Feeding of adult rats with 10 d of LPD increased 1-OHase (P<0·05) and suppressed 24-OHase (P<0·001) as well as VDR (P<0·05) mRNA expression. These results indicate that the increase in serum 1,25(OH)2D3 level in adult rats during short-term LPD treatment is likely to be mediated by a decrease in metabolic clearance via the down-regulation of both renal 24-OHase and VDR expression. The induction of renal 1-OHase mRNA expression in adult rats requires longer duration of LPD treatment than in younger rats.

Type
Research Article
Copyright
Copyright © The Nutrition Society 2005

References

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