Prednisolone-induced Ca2+malabsorption is caused by diminished expression of the epithelial Ca2+channel TRPV6

Abstract

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 Ca2+in the intestine is supposed to play an important role in the etiology of low BMD. To elucidate the mechanism of glucocorticoid-induced Ca2+malabsorption, the present study investigated the effect of prednisolone on the expression and activity of proteins responsible for active intestinal Ca2+absorption including the epithelial Ca2+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 vivo45Ca2+absorption assay indicated that intestinal Ca2+absorption was diminished after prednisolone treatment. We showed decreased duodenal TRPV6 and calbindin-D9KmRNA 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 Ca2+transport proteins are predominantly localized in the first 2 cm of the duodenum. Furthermore, serum Ca2+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 Ca2+absorption capacity through diminished duodenal expression of the active Ca2+transporters TRPV6 and calbindin-D9Kindependent of systemic 1,25(OH)2D3.