Simonoska Rusana, Stenberg Annika E, Duan Maoli, Yakimchuk Konstantin, Fridberger Anders, Sahlin Lena, Gustafsson Jan-Ake, Hultcrantz Malou
Department of Otorhinolaryngology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
J Endocrinol. 2009 Jun;201(3):397-406. doi: 10.1677/JOE-09-0060. Epub 2009 Mar 17.
There are well known differences between males and females in hearing. In the present study, the role of estrogen receptor-beta (ER-beta; listed as ESR2 in the MGI Database) in hearing was investigated by comparing hearing and morphology of the inner ear in ER-beta knock-out mice (ER-beta(-/-)) with that of wild-type (WT) littermates. Hearing was analyzed with auditory brainstem response audiometry at 3 and 12 months. The ER-beta(-/-) mice were deaf at 1 year of age, and the morphological analysis showed absence of hair cells and loss of the whole organ of Corti initiated in the basal turn of the cochlea. Furthermore, in ER-beta(-/-), but not in WT mice, the spiral ganglion was lacking many of its neurons. Immunostaining showed the presence of both ER-alpha (listed as ESR1 in the MGI Database) and ER-beta in the nuclei of some neurons in the inner ear in WT mice, but no ER-beta was found in the ER-beta(-/-) mice as expected. ER-alpha staining was predominant in the nuclei of large neurons and ER-beta in nuclei of small neurons and fibroblasts. These results reveal that both ERs are present in the inner ear at specific localizations suggesting subtype-specific functions. It is concluded that ER-beta is important for the prevention of age-related hearing loss. These findings strengthen the hypothesis that estrogen has a direct effect on hearing functions.
男性和女性在听力方面存在众所周知的差异。在本研究中，通过比较雌激素受体β（ER-β；在MGI数据库中列为ESR2）基因敲除小鼠（ER-β(-/-)）与野生型（WT）同窝小鼠的听力和内耳形态，研究了ER-β在听力中的作用。在3个月和12个月时用听觉脑干反应测听法分析听力。ER-β(-/-)小鼠在1岁时失聪，形态学分析显示耳蜗基底转开始出现毛细胞缺失和整个柯蒂器丧失。此外，在ER-β(-/-)小鼠而非WT小鼠中，螺旋神经节缺少许多神经元。免疫染色显示WT小鼠内耳一些神经元的细胞核中同时存在ER-α（在MGI数据库中列为ESR1）和ER-β，但正如预期的那样，在ER-β(-/-)小鼠中未发现ER-β。ER-α染色在大神经元的细胞核中占主导，而ER-β在小神经元和成纤维细胞的细胞核中占主导。这些结果表明，两种雌激素受体在内耳中特定定位存在，提示具有亚型特异性功能。得出的结论是，ER-β对预防年龄相关性听力损失很重要。这些发现强化了雌激素对听力功能有直接影响这一假说。
