Blocking the glucocorticoid receptor with RU-486 does not prevent glucocorticoid control of autoimmune mouse hearing loss.

Audiology & Neuro-otology
Dennis R Trune, J Beth Kempton

Abstract

Glucocorticoids effectively manage autoimmune hearing loss, although the cochlear mechanisms involved are unknown. Previous studies of steroid-responsive hearing loss in autoimmune (lupus) mice showed glucocorticoids and mineralocorticoids were equally effective, suggesting the ion homeostasis functions of glucocorticoids may be as relevant as immunosuppression for control of autoimmune-induced inner ear disease. Therefore, to better characterize the role of the glucocorticoid receptor in autoimmune hearing loss therapy, its function was blocked with the antagonist RU-486 (mifepristone) during glucocorticoid (prednisolone) treatments. Following baseline auditory brainstem response (ABR) thresholds, MRL/MpJ-Fas(lpr) autoimmune mice were implanted with pellets providing combinations of 1.25 mg/kg of RU-486, 4 mg/kg of prednisolone, or their respective placebos. After 1 month, animals were retested with ABR and blood was collected for immune complex analyses. Mice receiving no prednisolone (placebo + placebo and placebo + RU-486) showed continued declines in hearing. On the other hand, mice receiving prednisolone (prednisolone + placebo and prednisolone + RU-486) had significantly better hearing (p < 0.05) than the non-prednisolon...Continue Reading

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Citations

Aug 10, 2010·Current Opinion in Otolaryngology & Head and Neck Surgery·Dennis R Trune
Sep 10, 2010·Current Opinion in Otolaryngology & Head and Neck Surgery·Mohamed Hamid
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Sep 10, 2010·Current Opinion in Otolaryngology & Head and Neck Surgery
Sep 13, 2021·Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology·Lacey NelsonMichael Hoa

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