Expression of the human glucocorticoid receptor alpha and beta isoforms in human respiratory epithelial cells and their regulation by dexamethasone

Am J Respir Cell Mol Biol. 2001 Jan;24(1):49-57. doi: 10.1165/ajrcmb.24.1.4024.


Two isoforms of the human glucocorticoid receptor (hGR) have been described, hGRalpha and hGRbeta. We analyzed the expression and regulation of both hGR isoforms in human respiratory epithelial cells (BEAS-2B, A549, and primary nasal epithelial cells). In BEAS-2B cells, the expression of hGRalpha messenger RNA (mRNA) was much higher than that of hGRbeta mRNA. Dexamethasone (DEX) (10(-6) M) downregulated hGRalpha mRNA at 6 and 24 h (55 +/- 8 and 58 +/- 5% of control, respectively; P < 0.01), whereas it decreased hGRbeta mRNA only at 6 h (55 +/- 7% of control; P < 0.01). Downregulation of hGRalpha and hGRbeta mRNAs occurred even in the presence of cycloheximide. Actinomycin-D studies revealed that DEX enhanced the stabilization of hGRalpha and hGRbeta messages. hGRalpha but not hGRbeta protein was detected in BEAS-2B, A549, and nasal epithelial cells. After 24 h of incubation, 10(-6) M DEX decreased the expression of hGRalpha protein in BEAS-2B, A549, and nasal epithelial cells (16 +/- 4, 14 +/- 4, and 28 +/- 7% of control, respectively; P < 0.01). These results suggest that in respiratory epithelial cells: (1) hGRalpha is much more expressed than hGRbeta at both the mRNA and protein levels; (2) hGRalpha is downregulated by corticosteroids both in cell lines (BEAS-2B, A549) and in nasal primary cells; and (3) transcriptional, post-transcriptional, and post-translational mechanisms appear to be involved in the regulation of hGR expression by corticosteroids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • COS Cells
  • Cell Line
  • Dexamethasone / pharmacology*
  • Dose-Response Relationship, Drug
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Gene Expression Regulation / drug effects
  • Humans
  • Nasal Mucosa / cytology
  • Nasal Mucosa / drug effects
  • Nasal Mucosa / metabolism
  • Protein Isoforms / biosynthesis
  • RNA, Messenger / metabolism
  • Receptors, Glucocorticoid / biosynthesis*
  • Receptors, Glucocorticoid / genetics
  • Respiratory Mucosa / cytology
  • Respiratory Mucosa / drug effects*
  • Respiratory Mucosa / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction


  • Protein Isoforms
  • RNA, Messenger
  • Receptors, Glucocorticoid
  • glucocorticoid receptor alpha
  • glucocorticoid receptor beta
  • Dexamethasone