Estradiol Treatment and Hormonal Fluctuations During the Estrous Cycle Modulate the Expression of Estrogen Receptors in the Auditory System and the Prepulse Inhibition of Acoustic Startle Response
Estradiol Treatment and Hormonal Fluctuations During the Estrous Cycle Modulate the Expression of Estrogen Receptors in the Auditory System and the Prepulse Inhibition of Acoustic Startle Response
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DOI：
10.1210/en.2012-1416
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发表时间：
2012-09-01
期刊：
影响因子：
4.8
通讯作者：
Canlon, Barbara
中科院分区：
文献类型：
--
作者：
Charitidi, Konstantina;Meltser, Inna;Canlon, Barbara
雌激素对听力的影响是跨物种记录的，但负责的分子机制尚不清楚。雌激素受体（ER）在整个听觉系统中的存在为雌激素对听觉功能的直接影响提供了一条潜在的途径，但人们对每种ER的表达如何受到身体整体激素状态的调节知之甚少。在本研究中，我们确定了卵巢切除术和慢性17 β -雌二醇治疗对小鼠外周（耳蜗）和中央（下丘脑）听觉结构中ER α和ER β mRNA和蛋白表达的影响，以及通过声惊吓反应（ASR）、脉冲前抑制（PPI）和惊吓反应习惯化对听觉相关行为的影响。β -雌二醇治疗可下调ER α，但不能下调ER β，并可增加PPI和ASR潜伏期。ASR的大小和习惯程度均不受影响。此外，我们分析了整个发情周期（发情前期、发情期、发情期和退情期）内耳ER mRNA和蛋白的表达，发现循环雌激素与ER α表达呈负相关，而ER β表达稳定。我们的研究结果表明，内质网不仅存在于外周和中枢听觉系统中，而且循环雌激素水平下调内质网α在听觉系统中的表达，影响PPI和ASR潜伏期，提示内质网α作为激素诱导的听觉系统和行为调节剂的关键作用。（内分泌学153:4412-4421,2012）
Estrogens' effects on hearing are documented across species, but the responsible molecular mechanisms remain unknown. The presence of estrogen receptors (ER) throughout the auditory system offers a potential pathway of direct estrogenic effects on auditory function, but little is known about how each ER's expression is regulated by the overall hormonal status of the body. In the present study, we determined the effects of ovariectomy and chronic 17 beta-estradiol treatment on mRNA and protein expression of ER alpha and ER beta in peripheral (cochlea) and central (inferior colliculus) auditory structures of mice, as well as on auditory-related behavior using the acoustic startle response (ASR), prepulse inhibition (PPI), and habituation of the startle response. 17 beta-Estradiol treatment down-regulated ER alpha but not ER beta and increased PPI and latency of the ASR. Neither the magnitude nor the habituation of ASR was affected. Furthermore, ER's mRNA and protein expression in the inner ear were analyzed throughout the estrous cycle (proestrus, estrus, metestrus, and diestrus), revealing a negative correlation of circulating estrogens with ER alpha expression, whereas ER beta was stable. Our findings show that ER not only are present in both the peripheral and central auditory system but also that circulating estrogen levels down-regulate ER alpha expression in the auditory system and affect PPI and the latency of ASR, suggesting a key role of ER alpha as a hormone-induced modulator of the auditory system and behavior. (Endocrinology 153: 4412-4421, 2012)