title: Hydrocortisone and deflazacort induce different effects on vitamin D receptor level increase produced by 1,25-dihydroxyvitamin D3 in rat osteoblast-like UMR-106 cells.
abstract: OBJECTIVE
  The homologous upregulation produced by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on vitamin D receptor (VDR) levels, and the effects produced by the heterologous agents hydrocortisone or deflazacort, alone or in conjunction with this vitamin D metabolite, were studied in rat osteoblastic UMR-106 osteosarcoma cells.
  
  
  METHODS
  VDR were determined by binding analysis (Bmax and dissociation constant). VDR mRNA expression levels were measured by Northern blot analysis.
  
  
  RESULTS
  Incubation with 10 nM 1,25(OH)2D3 produced a significant increase in Bmax with respect to ethanol-treated cells (100.2 +/- 13.2 vs 11.4 +/- 4.8 fmol 3H-1,25(OH)2D3 bound/mg protein) together with a significant increase in VDR mRNA expression (483 +/- 170% vs 100%). The addition of 10 nM hydrocortisone to 1,25(OH)2D3 produced a significant decrease in Bmax (from 100.2 +/- 13.2 to 44 +/- 5.6), with mRNA levels similar to those of basal conditions (116 +/- 25% vs 100%). However, the addition of 10 nM deflazacort did not reduce the activation in Bmax produced by 1,25(OH)2D3 (92.4 +/- 16 vs 100.2 +/- 13.2), maintaining the increase in mRNA levels (430 +/- 10% vs 483 +/- 170%). If 10 nM hydrocortisone or 10 nM deflazacort was added to UMR-106 cells without 1,25(OH)2D3, a similar increase was observed in Bmax with respect to basal conditions (20.4 +/- 1.3 or 20.9 +/- 1.6 vs 11.4 +/- 4.8 in control cells), but hydrocortisone did not produce any significant variation in mRNA VDR levels, while deflazacort itself produced an increase in VDR mRNA expression.
  
  
  CONCLUSIONS
  Our findings of different actions produced by hydrocortisone and deflazacort on the increase of VDR levels produced by 1,25(OH)2D3 could explain some of the different actions produced by both antiinflammatory medications on bone metabolism.
authors.affiliation: Biochemistry Laboratory, Bone Pathophysiology Section, and Immunology Section, Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Guerrero
authors.forename: Concepción
authors.initials: C
authors.lastname: de la Piedra
authors.forename: Emma
authors.initials: E
authors.lastname: Teixeiro
authors.forename: Rafael
authors.initials: R
authors.lastname: Bragado
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Traba
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002117:Calcitriol / Q000378:metabolism / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D006854:Hydrocortisone / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011282:Pregnenediones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*; D014316:Tritium
chemical_list: D000893:Anti-Inflammatory Agents; D002120:Calcium Channel Agonists; D011282:Pregnenediones; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D014316:Tritium; D002117:Calcitriol; C021988:deflazacort; D006854:Hydrocortisone