Estrogenic regulation of systemic vocal fold dehydration

项目摘要 雌激素的一个核心作用是调节体内的水合平衡。身体（全身）水合作用减少， 引起全身声带脱水。系统性声带脱水改变了组织的生物学特性。 然而，雌激素在调节系统性声带的这些生物学变化中的重要性， 脱水情况不明。我们通过研究这些重要的临床和理论问题， 转录组、蛋白质组、组织形态学和超声发声结果的研究设计， 小心地操纵荷尔蒙状态和水合状态。我们还将研究雌激素对 血管几何形状和血液流动到喉后的相互作用，系统性脱水与改变 荷尔蒙状态我们使用大鼠动物模型进行这些研究，因为该模型允许稳健和严格的 控制水合作用和激素水平。因为雌激素是重要的，无论生物性别， 将包括雄性和雌性大鼠。为了检查荷尔蒙丢失和替代的影响，我们将 测量生殖器官被手术切除（卵巢切除和 睾丸切除的大鼠）和当递送雌二醇替代雌激素时。全身性脱水 通过限制水的平移范例诱导5天。可以自由饮水的动物将被 作为脱水的对照。在16个动物群体中，我们的第一个目标是量化激素损失的影响， 声带脱水的分子和组织学特征以及雌二醇替代的影响 这些签名。由于激素受体在声带粘膜中的位置不同， 肌肉，这些组织层具有独特的细胞组织和生物力学特性，声带 分别检查粘膜和肌肉。我们的第二个目标是研究激素与 状态和脱水的超声波发声。我们的第三个目标是研究荷尔蒙对 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、组织学和功能研究，以及血流动力学的机制研究， 修改，这一全面的建议，旨在摆脱基本洞察到雌激素的影响， 声带脱水生物学需要这些数据来推动与声乐相关的临床建议 折叠生理条件下改变水化和激素状态。

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.