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


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.


RESULTS
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.


CONCLUSIONS
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.
Kim
Man-Hee
MH
Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, 361-763 Republic of Korea.
Lee
Geun-Shik
GS
Jung
Eui-Man
EM
Choi
Kyung-Chul
KC
Jeung
Eui-Bae
EB
D000042:Absorption / Q000187:drug effects; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects*; D064026:Calbindins; D002118:Calcium / Q000097:blood / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics; D003907:Dexamethasone / Q000009:adverse effects*; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000009:adverse effects*; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009929:Organ Size; D010280:Parathyroid Glands / Q000033:anatomy & histology / Q000187:drug effects; D010281:Parathyroid Hormone / Q000097:blood; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics; D064030:S100 Calcium Binding Protein G / Q000235:genetics; D019831:Sodium-Calcium Exchanger / Q000235:genetics; D050916:TRPV Cation Channels / Q000235:genetics
D000893:Anti-Inflammatory Agents; D064026:Calbindins; D015220:Calcium Channels; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D010281:Parathyroid Hormone; D064030:S100 Calcium Binding Protein G; C576507:S100g protein, mouse; D019831:Sodium-Calcium Exchanger; D050916:TRPV Cation Channels; C492240:Trpv5 protein, mouse; C446923:Trpv6 protein, mouse; C110374:sodium-calcium exchanger 1; D003907:Dexamethasone; D053499:Plasma Membrane Calcium-Transporting ATPases; D002118:Calcium