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

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) 2 D 3 ) as well as renal 25-hydroxyvitamin D 3 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) 2 D 3 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) 2 D 3 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) 2 D 3 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.