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Life Sci. 2009 Jul 17;85(3-4):146-52. doi: 10.1016/j.lfs.2009.05.013. Epub 2009 May 31.

The negative effect of dexamethasone on calcium-processing gene expressions is associated with a glucocorticoid-induced calcium-absorbing disorder.

Author information

1
Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, 361-763 Republic of Korea.

Abstract

AIMS:

Although dexamethasone (Dex) is used widely as an anti-inflammatory and immunosuppressive drug, Dex appears to have severe side-effects, including osteoporosis. This study determined the effects of Dex on duodenal and renal expressions of the calcium-processing genes transient receptor potential cation channel, subfamily V, member 5/6 (TRPV5/6), calbindin-D9k/-D28k (CaBP-9k/28k), Na+/Ca2+ exchanger 1 (NCX1), and plasma membrane Ca(2+)-ATPase (PMCA) 1b.

MAIN METHODS:

Mice were injected subcutaneously with Dex for 1 or 5 days. The mRNA and protein expression levels of these calcium-processing genes were measured by real-time PCR and immunohistochemistry/immunoblot analysis, respectively. In addition, serum parathyroid hormone (PTH) levels were measured following Dex treatments.

KEY FINDINGS:

Treatment with Dex for 24 h resulted in the inductions of duodenal TRPV6, CaBP-9k and PMCA1b transcripts and renal TRPV5, CaBP-9k, and NCX1 transcripts, while it reduced the transcription of renal TRPV6. Although the expressional changes were weak, duodenal expressions of glucocorticoid receptor (GR), the vitamin D receptor (VDR), and renal expressions of the parathyroid hormone receptor (PTHR) and VDR were increased following 24 h treatment with Dex. A five-day treatment with Dex reduced the transcriptional levels of duodenal TRPV6 and CaBP-9k by 60%. Transcripts for VDR and GR in the duodenum increased marginally.

SIGNIFICANCE:

These results suggest that the expressions of TRPV6 and CaBP-9k in the duodenum appear to be a major regulatory target for glucocorticoids (GCs), and may be involved in the negative regulation of calcium absorption in GC-induced osteoporosis (GIO). The transcriptional regulation of TRPV6 and CaBP-9k in the duodenum seems complex given that there is an increase at 1-day treatment followed by a decrease at 5-day treatment.

PMID:
19490920
DOI:
10.1016/j.lfs.2009.05.013
[Indexed for MEDLINE]

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