Distribution of Glucocorticoid Receptors and 11β-Hydroxysteroid Dehydrogenase Isoforms in the Human Inner Ear

Abstract

Glucocorticoids (GCs) are widely used as a therapeutic modality for the inner ear disorders including Ménière's disease (MD). The concentration of GCs in the target cells is known to be regulated by 11β-hydroxysteroid dehydrogenase (11β-HSD), an enzyme complex responsible for the conversion of hormonally active cortisol into inactive cortisone. There is no morphologic indication of glucocorticoid receptors (GRs) and 11β-HSD isoforms (11β-HSD1 and 2) in human inner ear. The objectives of this study are to determine whether GRs and the isoforms of 11β-HSD are present in human inner ear tissues and to reveal their precise distribution. This study investigated the expression of GRs and 11β-HSD isoforms (11β-HSD1 and 2) in the human inner ear. In humans, immunostaining of GRs, 11β-HSD1, and 11β-HSD2 was performed in the stria vascularis (SV) and the vestibular tissues, whereas in the cochlear tissues except for the SV, only GRs were investigated. Immunoreactivity of GRs was detected in the SV, outer hair cells, inner hair cell, spiral ligament, Reissner's membrane, vestibular hair cells, vestibular nerve, transitional cells, and dark cells of the crista ampullaris. 11β-HSD1 was observed in the SV, the apical area of the vestibular hair cells, the transitional cells, and the dark cells. However, no immunoreactivity of 11β-HSD2 was observed. Those data indicate that different local steroid regulation by GRs and the isoforms of 11β-HSD is present in various parts of the human inner ear tissues and that the tissues are a direct therapeutic target of glucocorticoids in the inner ear diseases.