Effects of neuroactive steroids on cochlear hair cell death induced by gentamicin
Effects of neuroactive steroids on cochlear hair cell death induced by gentamicin
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DOI：
10.1016/j.steroids.2011.07.014
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发表时间：
2011-12-11
期刊：
影响因子：
2.7
通讯作者：
Hara, Akira
中科院分区：
文献类型：
--
作者：
Nakamagoe, Mariko;Tabuchi, Keiji;Hara, Akira
性类固醇激素作为神经活性类固醇，具有非生殖作用。我们曾报道17β-雌二醇(βE_2)对庆大霉素(GM)耳毒性有保护作用。在本研究中，我们研究了β-E2对GM耳毒性的保护作用是否由雌激素受体(ER)介导，以及其他雌激素(17-α-雌二醇(α-E2)、雌酮(E1)和雌三醇(E3))和其他神经活性类固醇(脱氢表雄酮(DHEA)和孕酮(P))是否具有类似的保护作用。分离SD大鼠Corti器基底角，在含100 mU GM的培养液中培养48h，观察β-雌二醇和选择性雌激素受体拮抗剂ICI182,780的作用。此外，还利用该培养系统对其他雌激素、DHEA和P的作用进行了检测。比较不同染毒组大鼠外毛细胞的脱失情况。βE_2对GM耳毒性具有保护作用，但其保护作用可被ICI 182、780拮抗。阿尔法E2、E1和E3也可以保护毛细胞免受庆大霉素的耳毒性。DHEA显示出保护作用：然而，添加ICI 182,780并不影响毛细胞丢失。P对GM诱导的外毛细胞死亡没有任何影响。本研究结果提示雌激素和脱氢表雄酮对转基因耳毒性有保护作用。ER拮抗剂的研究结果还表明，β-E2的保护作用是通过ER介导的，而DHEA的保护作用与其转化为雌激素并与ER结合无关。对神经活性类固醇的进一步研究可能会带来关于耳蜗保护的新见解。(C)2011 Elsevier Inc.保留所有权利。
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.