Estrogenic regulation of systemic vocal fold dehydration

项目总结 雌激素的核心作用是调节体内的水分平衡。身体(全身)水合作用减少， 导致全身性声带脱水。全身性声带脱水会改变组织的生物学特性。 然而，雌激素在调节系统声带的这些生物学变化中的重要性 脱水情况仍不得而知。我们通过研究这个重要的临床和理论问题 在一项研究设计中，转录组、蛋白质组、组织形态和超声发声结果 小心控制荷尔蒙状态和水合状态。我们还将研究雌激素对 全身性脱水与改变的相互作用后血管几何和流向喉部的血流 荷尔蒙状态。我们使用大鼠动物模型进行这些研究，因为这个模型允许健壮和严谨 控制水分和荷尔蒙水平。因为雌激素是重要的，与生理性别无关，两者 雄鼠和雌鼠将被包括在内。为了检查荷尔蒙丢失和替换的影响，我们将 测量手术切除生殖器官后的结果(卵巢摘除和 切除的大鼠)和雌激素替代雌二醇的时间。全身脱水将是 由5天限水的翻译范式诱导。免费获得水的动物将为 作为脱水的控制。在16个动物组中，我们的第一个目标是量化荷尔蒙丢失的影响 声带脱水的分子和组织学特征及雌激素替代治疗的影响 在这些签名上。因为激素受体不同地分布在声带粘膜和 肌肉，这些组织层具有不同的细胞组织和生物力学特性，声带 分别对粘膜和肌肉进行检查。我们的第二个目标是研究荷尔蒙的相互作用 超音波发声的现状与脱水。我们的第三个目标是检查荷尔蒙的影响 状态和脱水对血管几何形状、血流以及这些变化的生理后果的影响。 通过结合分子、组织和功能研究以及血流动力学的机制研究 修改，这项全面的提案试图对雌激素对 声带脱水生物学。需要这些数据来推动与声带有关的临床建议 在水合和荷尔蒙状态改变的情况下折叠生理学。

PROJECT SUMMARY A central role of estrogen is regulating hydration balance in the body. Decreases in body (systemic) hydration, cause systemic vocal fold dehydration. Systemic vocal fold dehydration alters the biology of the tissue. Nevertheless, the importance of estrogens in regulating these biological changes of systemic vocal fold dehydration remain unknown. We address this important clinical and theoretical issue by investigating the transcriptome, proteome, tissue morphology, and ultrasonic vocalization outcomes in a study design that carefully manipulates hormonal state and hydration state. We will also examine the effects of estrogen on the vascular geometry and blood flow to the larynx following the interaction of systemic dehydration with altered hormonal states. We use the rat animal model for these studies since this model allows for robust and rigorous control of hydration and hormonal levels. Because estrogen is important irrespective of biological sex, both male and female rats will be included. To examine the effects of hormonal loss and replacement, we will measure outcomes when reproductive organs have been surgically removed (ovariectomized and orchiectomized rats) and when estrogen replacement with estradiol is delivered. Systemic dehydration will be induced by a translational paradigm of water restriction for 5 days. Animals with free access to water will serve as controls for dehydration. Across 16 animal groups, our first goal is to quantify the effects of hormonal loss on the molecular and histologic signatures of vocal fold dehydration and the influence of estradiol replacement on these signatures. Because hormone receptors are differentially located across vocal fold mucosa and muscle, and these tissue layers have distinct cellular organization and biomechanical properties, the vocal fold mucosa and muscle are examined separately. Our second goal is to investigate the interaction of hormonal status and dehydration on ultrasonic vocalizations. Our third goal is to examine the influence of hormonal status and dehydration on vascular geometry, blood flow, and the physiologic consequences of these changes. By combining molecular, histological, and functional studies, and mechanistic investigations of hemodynamic modifications, this comprehensive proposal seeks to shed fundamental insight into the effects of estrogens on vocal fold dehydration biology. These data are needed to drive clinical recommendations pertaining to vocal fold physiology under conditions of altered hydration and hormonal states.