GRβ Regulates Glucocorticoid Resistance in Sudden Sensorineural Hearing Loss

Curr Pharm Biotechnol. 2021;22(9):1206-1215. doi: 10.2174/1389201021666201008163534.


Background: In recent years, the incidence of sudden deafness has gradually increased, with a very limited understanding of its etiology and pathogenesis. Glucocorticoids are the first choice of the treatment, but some hormone-resistant patients are not sensitive to glucocorticoid therapy. The pathogenesis is not yet known. In this study, we aim to construct the HEI-OC1 cell line stably overexpressing Glucocorticoid Receptor Beta (GRβ), and identify its exact role in the cases of glucocorticoidresistant sudden deafness.

Methods: We used the endotoxin lipopolysaccharide-stimulated cochlear hair cells (HEI-OC1) to investigate the relationship of inflammation factor IL-2, TNF alpha, and SRp30c with the high expression GRβ. We built a stable GRβ high expression HEI-OC1 cell line and clarified its effects on the therapeutic effect of dexamethasone. MTT assay, colony formation assay, CCK-8 assay, Western blot, and RT-qPCR were utilized for characterizations.

Results: Dexamethasone reduced the LPS-induced inflammatory response from HEI-OC1 cells (p<0.05), detected by MTT assay. Dexamethasone could protect HEI-OC1 cells, but its protective effect was weakened due to the transfection of SRp30c over-expression plasmid (p<0.05). The transfection of SRp30c over-expression plasmid in HEI-OC1 cells could elevate the expressions of GRβ (p<0.05).

Conclusion: We clarified the mechanisms of high expression of GRβ in glucocorticoid-resistant sudden sensorineural hearing loss, and proved that the inhibition of SRp30c may act as a new treatment way of glucocorticoid-resistant sudden sensorineural hearing loss.

Keywords: GRβ; Glucocorticoid resistance; LPS; SRp30c; dexamethasone; sudden sensorineural hearing loss.

MeSH terms

  • Cell Line
  • Cell Survival / drug effects
  • Dexamethasone / pharmacology
  • Drug Resistance / drug effects
  • Glucocorticoids / pharmacology*
  • Hair Cells, Auditory / cytology
  • Hair Cells, Auditory / drug effects
  • Hair Cells, Auditory / metabolism
  • Hearing Loss, Sensorineural / metabolism
  • Hearing Loss, Sensorineural / pathology
  • Humans
  • Interleukin-2 / genetics
  • Interleukin-2 / metabolism
  • Lipopolysaccharides / pharmacology
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / metabolism*
  • Serine-Arginine Splicing Factors / genetics
  • Serine-Arginine Splicing Factors / metabolism
  • Transfection
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation / drug effects*


  • Glucocorticoids
  • Interleukin-2
  • Lipopolysaccharides
  • Receptors, Glucocorticoid
  • SRSF9 protein, human
  • Tumor Necrosis Factor-alpha
  • glucocorticoid receptor beta
  • Serine-Arginine Splicing Factors
  • Dexamethasone