Cochlear Glucocorticoid Receptor and Serum Corticosterone Expression in a Rodent Model of Noise-induced Hearing Loss: Comparison of Timing of Dexamethasone Administration

• Published in: Scientific reports Vol. 9; no. 1; pp. 12646 - 11
• Main Authors: Lee, Seung-Hun, Lyu, Ah-Ra, Shin, Sun-Ae, Jeong, Seong-Hun, Lee, Sun-A, Park, Min Jung, Park, Yong-Ho
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.09.2019; Nature Publishing Group
• Subjects: 13; 13/21; 13/51; 38; 631/378/2619/1387; 692/308; 692/4017; 692/699/578; Adrenal cortex; Adrenal glands; Animal models; Animals; Auditory Threshold; Cell Survival; Cochlea; Cochlea - metabolism; Corticosterone; Corticosterone - blood; Cytokines; Cytokines - blood; Dexamethasone; Dexamethasone - administration & dosage; Dexamethasone - therapeutic use; Disease Models, Animal; Drug Administration Schedule; Epithelium - pathology; Evoked Potentials, Auditory, Brain Stem; Gene expression; Glucocorticoid receptors; Glucocorticoids; Hair Cells, Auditory - pathology; Hearing loss; Hearing Loss, Noise-Induced - blood; Hearing Loss, Noise-Induced - drug therapy; Hearing Loss, Noise-Induced - metabolism; Hearing Loss, Noise-Induced - physiopathology; Hearing protection; Humanities and Social Sciences; Inflammation; Inflammation Mediators - blood; Inner ear; Male; Menopause; Mice; multidisciplinary; Noise; Receptors, Glucocorticoid - genetics; Receptors, Glucocorticoid - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Science; Science (multidisciplinary); Steroids; Trauma
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-49133-w

Glucocorticoid (GC) is a steroid hormone secreted from the adrenal cortex in response to stress, which acts by binding to cytoplasmic glucocorticoid receptors (GRs). Dexamethasone (DEX) is a synthetic GC exhibiting immunosuppressive effects in both human and rodent models of hearing loss. While clinical evidence has shown the effectiveness of DEX for treatment of various inner ear diseases, its mechanisms of action and the optimal timing of treatment are not well understood. In the present study, intergroup comparisons were conducted based on the time point of treatment with DEX: (1) pretreatment; (2) posttreatment; and (3) pre&post-noise. The pre&post DEX treatment group showed a significant improvement in threshold shift at 1 day post-noise exposure as compared to the TTS (transient threshold shift)-only group at 8 and 16 kHz. Both TTS and PTS (permanent threshold shift) significantly reduced cochlear GR mRNA expression and increased serum corticosterone and cochlear inflammatory cytokines. The pre&post DEX treatment group showed a significant decrease in serum corticosterone level as compared to other DEX treatment groups and TTS-treated group at 3 days after acoustic trauma. Our results suggest that the timing of DEX administration differentially modulates systemic steroid levels, GR expression and cochlear cytokine expression.