Glucocorticoids decrease vitamin D receptor number and gene expression in human osteosarcoma cells.
The mechanisms by which glucocorticoids (GC) inhibit some actions of vitamin D [1,25-(OH)2D3] are not well understood, but there is growing evidence that GC alter vitamin D receptor (VDR) number. We studied the effects of dexamethasone (DEX) on VDR number and mRNA in the human osteosarcoma cell line, MG-63. The effects of DEX on 1,25-(OH)2D3 binding were examined by incubating confluent cells overnight in media without or with 10(-6) M DEX. DEX decreased VDR number (B max) by approximately 70% (110 versus 32 fmol/mg cellular protein, p less than 0.001) without significantly changing the apparent affinity (K'D) of 1,25-(OH)2D3 for its receptor (3.8 versus 2.2 x 10(-10) M, p greater than 0.05). Overnight incubation of MG-63 cells with DEX produced a time- and dose-responsive decrease in VDR mRNA compared to untreated controls (p less than 0.01). To determine the mechanism of the DEX-mediated decrease in VDR mRNA, the effect of DEX on VDR mRNA stability was studied. We found that the half-life for the VDR mRNA was approximately 5.7 h and was not significantly changed when the cells were incubated with DEX (approximately 6.3 h). We conclude that DEX decreases both VDR number and mRNA in MG-63 osteosarcoma cells. Since the half-life of VDR mRNA was not significantly modified by dexamethasone, glucocorticoids appear to decrease VDR mRNA by inhibiting VDR gene transcription or by affecting the processing of VDR mRNA.
Godschalk
M
M
Department of Internal Medicine, McGuire VA Medical Center, Richmond, Virginia.
Levy
J R
JR
Downs
R W
RW
D000199:Actins / Q000187:drug effects / Q000235:genetics; D015152:Blotting, Northern; D002117:Calcitriol / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006657:Histones / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007700:Kinetics; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000199:Actins; D006657:Histones; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D003907:Dexamethasone; D002117:Calcitriol