The interaction between GCs and their receptors is characterized by high selectivity and saturation. The efficacy of GCs may be closely associated with the expression level of GRs, which is confirmed in some diseases 
. We hypothesized that the level of GRs in the cochlea might be an important factor affecting the efficacy of GCs in treating SSNHL. In the present study, we found GR was expressed in both PBMCs and cochleae in guinea pigs, although its expression levels varied between test animals. Our results demonstrated that the expression level of GR mRNA and GR protein in PBMCs was positively correlated with that in the cochlea of normal healthy guinea pigs, and the GR level in PBMCs and the cochlea of healthy guinea pigs increased simultaneously after a short-term dexamethasone administration. This relationship has been also observed between PBMCs and the kidney 
. Therefore, the expression level of GR in PBMCs may be a predictive tool for distally assessing GR level in the cochlea. This finding establishes a proof of principle that the expression level of GR in PBMCs may be used to gauge predicted GR sensitivity in SSNHL, prognostically classifying patients who may be resistant to GCs, thus proactively implementing alternative therapies to avoid unnecessary side effects of GCs. However, GC insensitivity can also be attributable to loss of function mutations in the sequence of GR 
. Therefore, sequencing analyses to probe for mutations in GR may be a beneficial complementary diagnostic approach in patients with SSNHL.
The GR level in PBMCs and the cochlea of healthy guinea pigs increased simultaneously after a short-term dexamethasone administration, indicating that short-term systemic steroid treatment could positively regulate the expression of GR. Normally, GR expression is down-regulated by glucocorticoids as the result of a feedback protective mechanism. However, up-regulation of GR has been observed in nasal polyps after short term (2 weeks) oral and intranasal glucocorticoid treatment
. Under these conditions, up-regulation of GR may enhance the physiological effects of GCs and improve the individual stress responsiveness. Up-regulation of GR mRNA in the inferior colliculus after noise exposure may be associated with stress-induced transient hypersensitivity of the auditory system 
. However, the endogenous GCs in guinea pigs produced by stress under pathological states, as well as long-term GC application, could down-regulate the expression of GR 
. The results of the present study were obtained following the administration of a high dose of dexamethasone in normal, healthy guinea pigs. It should also be noted that dexamethasone has been shown to be a potent inhibitor of hypothalamic-pituitary-adrenal (HPA) axis 
. Therefore, additional studies that address the changes of GR expression levels after short-term systemic use of low doses of GCs under normal and pathological conditions and the effect of dexamethasone on normal plasmatic GC levels are still needed.
In Humans, the GR has two major isoforms, namely, GRα and GRβ. Up-regulation of both types of GR isoforms has been observed in the kidney of male mice 
and nasal polyps 
in response to GC treatment. While the role of GRα is well characterized, GRβ remains elusive. An association between GC insensitivity and increased GRβ expression has been reported in asthma, rheumatoid arthritis, and inflammatory bowel disease 
. In addition, some studies have shown that the content and translocation of GRs might be related to GC sensitivity 
. GRα has a widespread distribution and is responsible for the induction and repression of target genes, while GRβ has been proposed to act as a dominant negative regulator 
. Therefore, the ratio of GRα/GRβ expression is likely to be important to the GC responsiveness of various cells and tissues, and consistent with this model, GC resistance is associated with low GRα/GRβ ratios 
. Although both receptors are broadly distributed throughout the cellular framework of the inner ear, a clear relationship between the functional interplay and GRα/GRβ expression has not been established in the human auditory system 
. We were only able to analyze the total level of GR protein in this study, as specific antibodies against GRα or GRβ of guinea pig are not commercially available. Therefore, we were not able to specifically address which isoform of GR is predominately up-regulated in PBMCs and cochleae after administration of dexamethasone. Nevertheless, our observation of a positive correlation between PBMC GR and the population of cochlear GRs suggests that PBMC GR level might be a useful surrogate indicator for predicting cochlear GR level. In addition to GRs, mineralocorticoid receptors can also play important roles in GC signaling in cochleae 
. Therefore, future studies that differentiate between the transcriptional expression levels, mutational status, and translocation of GRα and GRβ and mineralocorticoid receptors in the cochlea may further enhance our ability to design and implement effective therapeutic strategies for treating SSNHL.