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

Am J Physiol Gastrointest Liver Physiol. 2007 Jan;292(1):G92-7. doi: 10.1152/ajpgi.00317.2006. Epub 2006 Aug 10.


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-D(9K), 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-D(9K) 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-D(9K) independent of systemic 1,25(OH)2D3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calbindins
  • Calcium / metabolism*
  • Calcium Channels / drug effects
  • Calcium Channels / genetics*
  • Calcium Radioisotopes
  • Disease Models, Animal
  • Duodenum / physiology
  • Duodenum / physiopathology
  • Gene Expression Regulation / drug effects
  • Intestinal Absorption*
  • Intestinal Mucosa / physiology*
  • Intestinal Mucosa / physiopathology
  • Malabsorption Syndromes / physiopathology*
  • Mice
  • Mice, Inbred C57BL
  • Polymerase Chain Reaction
  • Prednisolone / pharmacology*
  • S100 Calcium Binding Protein G / genetics
  • TRPV Cation Channels / drug effects
  • TRPV Cation Channels / genetics*


  • Calbindins
  • Calcium Channels
  • Calcium Radioisotopes
  • S100 Calcium Binding Protein G
  • TRPV Cation Channels
  • Trpv6 protein, mouse
  • Prednisolone
  • Calcium