Vitamin D receptor is required for dietary calcium-induced repression of calbindin-D9k expression in mice

Abstract: Calbindin (CaBP), the vitamin D-dependent calcium-binding protein, is believed to play an important role in intracellular calcium transport. The aim of this study was to investigate the effect of high dietary calcium on the expression of CaBP-D9k and CaBP-D28k in the presence and absence of a functional vitamin D receptor (VDR). Treatment with the HCa¿Lac diet containing 2% calcium, 1.5% phosphorus and 20% lactose reversed the hypocalcemia seen in adult VDR-null mice in 3 weeks but did not significantly change the blood ionized calcium in wild-type mice. This dietary treatment dramatically suppressed both the duodenal and the renal CaBP-D9k expression in wild-type mice at both mRNA and protein levels but had little effect on the expression of the same gene in VDR-null mice. Removal of this diet gradually restored the expression of CaBP-D9k to the untreated level in wild-type mice. Only moderate or little change in CaBP-D28k expression was seen in wild-type and VDR-null mice fed with the HCa¿Lac diet. The VDR content in the duodenum or kidney of wild-type mice was not altered by the dietary treatment. These results suggest that calcium regulates CaBP-D9k expression by modulating the circulating 1,25-dihydrxyvitamin D3 level and that VDR is thus required for the dietary calcium-induced suppression of CaBP-D9k expression. Calcium regulation of the CaBP-D9k level may represent an important mechanism by which animals maintain their calcium balance. [Copyright &y& Elsevier]