Adaptive responses of 25-hydroxyvitamin D3 1-alpha hydroxylase expression to dietary phosphate restriction in young and adult rats

Abstract

Regulation of vitamin D metabolism alters with age. The present study is undertaken to investigate if the loss of renal 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) production in response to dietary phosphate (P) restriction in adult rats is due to an alteration in the renal expression of 25-hydroxyvitamin D3 1-alpha hydroxylase (1-OHase). Young (4–6 weeks old) and adult (12–14 weeks old) male Sprague Dawley rats were fed either normal P (NPD) or low P diet (LPD) for 0–5 days. Basal expression of 1-OHase protein was higher in adult rats. Young rats, but not adult rats, significantly increased 1-OHase protein and mRNA expressions in response to LPD in a time-dependent manner. To determine if the stability of renal 1-OHase protein changes with LPD feeding, young and adult rats fed either NPD or LPD for 5 days were injected intravenously with cycloheximide (CHX), a protein synthesis inhibitor. CHX decreased 1-OHase protein expression in young rats fed NPD. However, CHX did not alter 1-OHase protein expression in young rats fed LPD nor in adult rats fed either diet. The results indicate that the stability of renal 1-OHase protein increased with age and that LPD increased its stability only in young rats.