Glucocorticoids differentially regulate expression of duodenal and renal calbindin-D9k through glucocorticoid receptor-mediated pathway in mouse model

Am J Physiol Endocrinol Metab. 2006 Feb;290(2):E299-307. doi: 10.1152/ajpendo.00232.2005. Epub 2005 Oct 11.


Dexamethasone (Dex) is a member of the glucocorticoids (GCs), and is broadly used as an anti-inflammatory medication. Continuous administration with GCs induces adverse effects and suffering in humans (i.e., osteoporosis) due to negative calcium balance derived from low re- and absorption in the duodenum and kidney. A cytosolic calcium-binding protein, calbindin-D9k (CaBP-9k), is dominantly expressed in the renal and intestinal tissues involved in calcium re- and absorption and plays an active role in calcium transport. In the present study, we employed adrenalectomized (ADX) and sham-treated (Sham) male mice to examine the effect of Dex on CaBP-9k gene expression in the duodenum and kidney. Dex significantly reduced the levels of duodenal CaBP-9k mRNA and protein, and it restored ADX-induced decrease in renal CaBP-9k protein compared with the level of Sham control. Dex treatment increased calcium and phosphate levels in the sera of both Sham and ADX mice. In a time course experiment, Dex significantly decreased duodenal CaBP-9k at the transcriptional and translational levels at 3 days, whereas it temporarily increased CaBP-9k mRNA and protein levels at 12 and 24 h. Altered CaBP-9k expression by Dex was completely reversed by mifepristone, an antagonist for the GC receptor (GR). In addition, duodenal CaBP-9k and GR were colocalized on the enterocyte (duodenocyte), supporting a role for GR in regulating CaBP-9k. In ovariectomized (OVX) and ADX female mice daily treated with Dex for 3 days, duodenal CaBP-9k was expressed at the same level as in male mice. Also, no cross-activity of progesterone and Dex on their receptors was observed. Taken together, these results indicate that mouse CaBP-9k gene may be regulated by Dex in a tissue-specific manner, and reduced duodenal CaBP-9k via the GR pathway may take part in negative calcium absorption of GC-induced osteoporosis, whereas renal CaBP-9k may not be involved in the regulation of calcium homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calbindins
  • Dexamethasone / administration & dosage*
  • Dose-Response Relationship, Drug
  • Duodenum / drug effects
  • Duodenum / metabolism*
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Glucocorticoids / administration & dosage
  • Kidney / drug effects
  • Kidney / metabolism*
  • Male
  • Mice
  • Models, Animal
  • Receptors, Glucocorticoid / metabolism*
  • S100 Calcium Binding Protein G / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology


  • Calbindins
  • Glucocorticoids
  • Receptors, Glucocorticoid
  • S100 Calcium Binding Protein G
  • S100G protein, human
  • S100g protein, mouse
  • Dexamethasone