Relationship of glucocorticoid receptor expression in peripheral blood mononuclear cells and the cochlea of guinea pigs and effects of dexamethasone administration

Abstract

Background: Glucocorticoids (GCs) are widely used to treat sudden sensorineural hearing loss (SSNHL) and significantly improve hearing. However, GC insensitivity has been observed in some patients of SSNHL.

Objective: To study the correlation between GR expression in peripheral blood mononuclear cells (PBMCs) and in the cochlea of guinea pigs at mRNA and protein levels.

Methods: One group of guinea pigs received dexamethasone (10 mg/kg/day) intraperitoneally for 7 consecutive days (dexamethasone group), and another group of guinea pigs received normal saline (control group). Real time PCR and Western blotting were used to detect the expression of GR mRNA and GR protein in PBMCs and the cochleae.

Results: The GR mRNA and GR protein were detected in both PBMCs and the cochlear tissue of guinea pigs. GR mRNA and GR protein levels in PBMCs were positively correlated with those in the cochlea. The expression of GR mRNA and GR protein was significantly increased in the dexamethasone group compared to the control group.

Conclusions: Levels of GR mRNA and GR protein in the PBMCs were positively correlated with those in the cochlea of guinea pigs. Systemic dexamethasone treatment can significantly up-regulate GR expression in PBMCs and in the cochlea. Measurement of the GR level in PBMCs could be used as an indicator of GR level in the cochlea.

Figure 1. The expression level of GR mRNA in PBMCs was significantly correlated with that in cochlea from both the control group (Fig. 1A, r = 0.818, p<0.01) and the dexamethasone group (Fig. 1B, r = 0.792, p<0.01).

Figure 2. Examples of the GR protein band in PBMCs and cochleae of representative guinea pigs from both the control group (Fig. 2A, C1, C2 and C3) and the dexamethasone group (Fig. 2B, D1, D2 and D3).

GAPDH was used as an endogenous control.

Figure 3. Relative GR protein levels (GR/GAPDH) in PBMCs and cochleae from both the control group and the dexamethasone group.

Dexamethasone administration synchronously up-regulated the GR protein levels in PBMCs and Cochleae in guinea pigs.

Figure 4. The GR protein level in PBMCs was significantly correlated with that observed in the cochleae from both the control group (Fig? 4A, r = 0.800, p<0.01) and the dexamethasone group (Fig? 4B, r = 0.858, p<0.01).