Effects of neuroactive steroids on cochlear hair cell death induced by gentamicin

As neuroactive steroids, sex steroid hormones have non-reproductive effects. We previously reported that 17 beta-estradiol (beta E2) had protective effects against gentamicin (GM) ototoxicity in the cochlea. In the present study, we examined whether the protective action of beta E2 on GM ototoxicity is mediated by the estrogen receptor (ER) and whether other estrogens (17 alpha-estradiol (alpha E2), estrone (E1), and estriol (E3)) and other neuroactive steroids, dehydroepiandrosterone (DHEA) and progesterone (P), have similar protective effects. The basal turn of the organ of Corti was dissected from Sprague-Dawley rats and cultured in a medium containing 100 mu M GM for 48 h. The effects of beta E2 and ICI 182,780, a selective ER antagonist, were examined. In addition, the effects of other estrogens, DHEA and P were tested using this culture system. Loss of outer hair cells induced by GM exposure was compared among groups. beta E2 exhibited a protective effect against GM ototoxicity, but its protective effect was antagonized by ICI 182, 780. alpha E2, E1, and E3 also protected hair cells against gentamicin ototoxicity. DHEA showed a protective effect: however, the addition of ICI 182,780 did not affect hair cell loss. P did not have any effect on GM-induced outer hair cell death. The present findings suggest that estrogens and DHEA are protective agents against GM ototoxicity. The results of the ER antagonist study also suggest that the protective action of beta E2 is mediated via ER but that of DHEA is not related to its conversion to estrogen and binding to ER. Further studies on neuroactive steroids may lead to new insights regarding cochlear protection. (C) 2011 Elsevier Inc. All rights reserved.