Expression and dexamethasone-induced nuclear translocation of glucocorticoid and mineralocorticoid receptors in guinea pig cochlear cells

Abstract

Glucocorticoids (GC) are powerful anti-inflammatory agents frequently used to protect the auditory organ against damage associated with a variety of conditions, including noise exposure and ototoxic drugs as well as bacterial and viral infections. In addition to glucocorticoid receptors (GC-R), natural and synthetic GC are known to bind mineralocorticoid receptors (MC-R) with great affinity. We used light and laser scanning confocal microscopy to investigate the expression of GC-R and MC-R in different cell populations of the guinea pig cochlea, and their translocation to different cell compartments after treatment with the synthetic GC dexamethasone. We found expression of both types of receptors in the cytoplasm and nucleus of sensory inner and outer hair cells as well as pillar, Hensen and Deiters cells in the organ of Corti, inner and outer sulcus cells, spiral ganglion neurons and several types of spiral ligament and spiral limbus cells; stria vascularis cells expressed mostly MC-R whereas fibrocytes type IV were positive for GC-R only. GC-R and MC-R were also localized at or near the plasma membrane of pillar cells and outer hair cells, whereas GC-R were found at or near the plasma membrane of Hensen cells only. We investigated the relative levels of receptor expression in the cytoplasm and the nucleus of Hensen cells treated with dexamethasone, and found they varied in a way suggestive of dose-induced translocation. These results suggest that the oto-protective effects of GC could be associated with the concerted activation of genomic and non-genomic, GC-R and MC-R mediated signaling pathways in different regions of the cochlea.