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Am J Physiol Gastrointest Liver Physiol 292: G92-G97, 2007. First published August 10, 2006; doi:10.1152/ajpgi.00317.2006
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HORMONES AND SIGNALING

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

Sylvie Huybers,1 Ton H. J. Naber,2 René J. M. Bindels,1 and Joost G. J. Hoenderop1

1Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre; and 2Departments of Gastroenterology, Radboud University Nijmegen Medical Centre and Internal Medicine, Hilversum Hospital, Nijmegen, The Netherlands

Submitted 18 July 2006 ; accepted in final form 5 August 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 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 vivo 45Ca2+ absorption assay indicated that intestinal Ca2+ 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 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-D9K independent of systemic 1,25(OH)2D3.

1,25-dihydroxyvitamin D3; duodenum; epithelial calcium channel 2; calcium transporter 1



Address for reprint requests and other correspondence: J. G. Hoenderop, 286 Cell Physiology, Radboud Univ. Nijmegen Medical Centre, P.O. Box 9101, NL-6500 HB Nijmegen, the Netherlands (e-mail: j.hoenderop{at}ncmls.ru.nl)




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