Effects of Glucocorticoids on the Inner Ear

Hypothesis: Recently, several lines of evidence have suggested that the inner ear is under hormonal control. It is likely that steroids have some influence on the inner ear.Background: Many clinicians have been empirically using steroids for the treatment of diseases associated with endolymphatic hydrops. The theoretical grounds for this are not clear, and there have been a number of debates on the effectiveness of steroid treatment. Furthermore, there are few reports on histological observations of the influences of steroids on the cochlea.Method: Fifteen guinea pigs (30 ears) were divided into three groups. In the control group, physiological saline solution was administered intra-peritoneally for 3 days. In two steroid groups, 40 mg/kg/day of hydrocortisone or 4 mg/kg/day of dexamethasone was administered intra-peritoneally for 3 days. Extension of Reissner's membrane and volume change of the scala media were checked 6 h after the last administration. The degree of Reissner's membrane extension and volumetric change of the scala media were quantitatively measured with the use of a video-digitizer.Results: We did not identify any distinct changes in the cochlea of the control group. In contrast, the extension of Reissner's membrane and endolymphatic hydrops were observed in the animals in the steroid groups. Statistical analysis revealed that Reissner's membrane extended significantly in the steroid groups, and that the volume of the scala media also increased significantly.Conclusion: This is the first report to investigate the effects of systemic administration of glucocorticoids on guineapig cochlea. The extension of Reissner's membrane and dilated endolymphatic space were evident in the steroid groups. However, the underlying mechanism of histological changes was not clear, marked care needs to be taken when administering steroids to patients with Meniere's disease whose histological feature is endolymphatic hydrops.

Insulin Receptor and Glucose Transporters in the Mammalian Cochlea

Insulin receptors are expressed on nerve cells in the mammalian brain, but little is known about insulin signaling and the expression of the insulin receptor (IR) and glucose transporters in the cochlea. We performed immunohistochemistry and gene/protein expression analysis to characterize the expression pattern of the IR and glucose transporters in the mouse organ of Corti (OC). We also performed glucose uptake assays to explore the action of insulin and the effects of pioglitazone, an insulin sensitizer, on glucose transport in the OC. Western blots of protein extracts from OCs showed high expression of IR and glucose transporter 3 (GLUT3). Immunohistochemistry demonstrated that the IR is specifically expressed in the supporting cells of the OC. GLUT3 was found in outer and inner hair cells, in the basilar membrane (BM), the stria vascularis (SV), Reissner’s membrane and spiral ganglion neurons (SGN). Glucose transporter 1 (GLUT1) was detected at low levels in the BM, SV and Reissner’s membrane, and showed high expression in the SGN. Fluorescence glucose uptake assays revealed that hair cells take up glucose and that addition of insulin (10 nM or 1 µM) approximately doubled the rate of uptake. Pioglitazone conferred a small but nonsignificant potentiation of glucose uptake at the highest concentration of insulin. Gene expression analysis confirmed expression of IR, GLUT1 and GLUT3 mRNA in the OC. Pioglitazone significantly upregulated IR and GLUT1 mRNA expression, which was further increased by insulin. Together, these data show that insulin-stimulated glucose uptake occurs in the OC and may be associated with upregulation of both the IR and GLUT1.