Prednisolone-induced Ca malabsorption is caused by diminished expression of the epithelial Ca channel TRPV6

Huybers S, Naber TH, Bindels RJ, Hoenderop JG. Prednisolone-induced Ca malabsorption is caused by diminished expression of the epithelial Ca channel TRPV6. Am J Physiol Gastrointest Liver Physiol 292: G92–G97, 2007. First published August 10, 2006; doi:10.1152/ajpgi.00317.2006.—Glucocorticoids, such as prednisolone, are often used in clinic because of their anti-inflammatory and immunosuppressive properties. However, glucocorticoids reduce bone mineral density (BMD) as a side effect. Malabsorption of Ca in the intestine is supposed to play an important role in the etiology of low BMD. To elucidate the mechanism of glucocorticoid-induced Ca malabsorption, the present study investigated the effect of prednisolone on the expression and activity of proteins responsible for active intestinal Ca absorption including the epithelial Ca channel TRPV6, calbindin-D9K, and the plasma membrane ATPase PMCA1b. Therefore, C57BL/6 mice received 10 mg/kg body wt prednisolone daily by oral gavage for 7 days and were compared with control mice receiving vehicle only. An in vivo Ca absorption assay indicated that intestinal Ca absorption was diminished after prednisolone treatment. We showed decreased duodenal TRPV6 and calbindin-D9K mRNA and protein abundance in prednisolone-treated compared with control mice, whereas PMCA1b mRNA levels were not altered. Importantly, detailed expression studies demonstrated that in mice these Ca transport proteins are predominantly localized in the first 2 cm of the duodenum. Furthermore, serum Ca and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] concentrations remained unchanged by prednisolone treatment. In conclusion, these data suggest that prednisolone reduces the intestinal Ca absorption capacity through diminished duodenal expression of the active Ca transporters TRPV6 and calbindin-D9K independent of systemic 1,25(OH)2D3.