Meltser Inna, Tahera Yeasmin, Simpson Evan, Hultcrantz Malou, Charitidi Konstantina, Gustafsson Jan-Ake, Canlon Barbara
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
J Clin Invest. 2008 Apr;118(4):1563-70. doi: 10.1172/JCI32796.
The hormone estradiol affects the auditory system both by itself and by its interaction with neuroprotective factors. In this study, we examined the role of estrogen receptors (ERs) in response to auditory trauma. We found a ligand-dependent protective role for ERbeta in the auditory system by investigating mice deficient in ERalpha (ERKO mice), ERbeta (BERKO mice), and aromatase (ARKO mice). Basal auditory brainstem response (ABR) thresholds were similar in all animals. An acoustic trauma causing a temporary hearing loss raised ABR thresholds in male and female BERKO and ARKO mice compared with WT and ERKO mice. The ERalpha-selective agonist, propyl(1H) pyrazole-1,3,5-triyl-trisphenol (PPT), partially protected ARKO mice from trauma, while the ERbeta-selective agonist, 2,3-bis (4-hydroxyphenyl)-propionitrile (DPN), protected WT and ARKO mice. Immunohistochemistry and western blotting confirmed the expression of ERbeta in cochlea of WT males and females. Levels of brain-derived neurotrophic factor (BDNF), a neuroprotective peptide that can be induced by estrogen, was lower in BERKO and ARKO mice compared with WT. DPN treatment increased BDNF expression in ARKO mice. These data indicate ERbeta-mediated neuroprotection involving BDNF in the auditory system of males and females.
雌激素二醇自身及其与神经保护因子的相互作用都会影响听觉系统。在本研究中，我们检测了雌激素受体（ERs）在应对听觉创伤中的作用。通过研究缺乏ERα（ERKO小鼠）、ERβ（BERKO小鼠）和芳香化酶（ARKO小鼠）的小鼠，我们发现ERβ在听觉系统中具有配体依赖性保护作用。所有动物的基础听觉脑干反应（ABR）阈值相似。与野生型（WT）和ERKO小鼠相比，导致暂时性听力损失的声创伤使雄性和雌性BERKO和ARKO小鼠的ABR阈值升高。ERα选择性激动剂丙基（1H）吡唑-1,3,5-三基三苯酚（PPT）部分保护ARKO小鼠免受创伤，而ERβ选择性激动剂2,3-双（4-羟基苯基）丙腈（DPN）则保护WT和ARKO小鼠。免疫组织化学和蛋白质印迹证实了WT雄性和雌性小鼠耳蜗中ERβ的表达。与WT相比，BERKO和ARKO小鼠中可由雌激素诱导的神经保护肽脑源性神经营养因子（BDNF）水平较低。DPN处理增加了ARKO小鼠中BDNF的表达。这些数据表明，在雄性和雌性的听觉系统中，ERβ介导的神经保护作用涉及BDNF。
