Estrogenic regulation of systemic vocal fold dehydration

全身声带脱水的雌激素调节

• 批准号: 10420218
• 负责人: Abigail Cox
• 金额: $ 63.08万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10420218
• 关键词: Acoustics; Address; Adult; Affect; Air Movements; Animal Model; Animals; Automobile Driving; Behavioral; Biological; Biology; Biomechanics; Blood; Blood Vessels; Blood flow; Clinical; Data; Dehydration; Desire for food; Discipline; Doppler Ultrasound; Equilibrium; Estradiol; Estrogen Receptors; Estrogen Replacements; Estrogens; Exposure to; Female; Food; Geometry; Goals; Gonadal Steroid Hormones; Histologic; Histology; Hormonal; Hormone Receptor; Hormones; Hydration status; Investigation; Knowledge; Larynx; Magnetic Resonance Angiography; Measures; Mechanical Stress; Menopause; Modeling; Modification; Molecular; Molecular Profiling; Morphology; Mucous Membrane; Muscle; National Institute on Deafness and Other Communication Disorders; Operative Surgical Procedures; Organ; Outcome; Outcome Measure; Physiological; Physiology; Placebos; Positioning Attribute; Property; Proteome; Publishing; Rattus; Recommendation; Regulation; Research; Research Design; Rewards; Role; Strategic Planning; Study models; Tissues; Ultrasonics; Vascular blood supply; Voice; Water; adverse outcome; awake; behavioral outcome; biological sex; clinically significant; estrogenic; functional outcomes; hemodynamics; in vivo; innovation; insight; intersectionality; laser capture microdissection; male; protective effect; reproductive organ; response; sex; transcriptome; vocal cord; vocalization; xenoestrogen

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.

项目概要 雌激素的核心作用是调节体内的水合平衡。身体（全身）水合作用减少， 导致全身声带脱水。全身声带脱水会改变组织的生物学特性。 尽管如此，雌激素在调节全身声带的这些生物学变化中的重要性 脱水情况仍未知。我们通过研究来解决这个重要的临床和理论问题 研究设计中的转录组、蛋白质组、组织形态和超声发声结果 仔细控制荷尔蒙状态和水合状态。我们还将研究雌激素对 全身脱水与改变的相互作用后血管几何形状和流向喉部的血流 荷尔蒙状态。我们使用大鼠动物模型进行这些研究，因为该模型允许稳健且严格的 控制水分和荷尔蒙水平。因为无论生物性别如何，雌激素都很重要，因此 将包括雄性和雌性大鼠。为了检查荷尔蒙损失和替代的影响，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）以及当用雌二醇替代雌激素时。将会出现全身性脱水 由5天限水转化范式诱导。可以自由饮水的动物将提供服务 作为脱水的控制。在 16 个动物群体中，我们的首要目标是量化荷尔蒙损失的影响 声带脱水的分子和组织学特征以及雌二醇替代的影响 在这些签名上。因为激素受体在声带粘膜上的分布存在差异， 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 粘膜和肌肉分别检查。我们的第二个目标是研究荷尔蒙的相互作用 超声波发声的状态和脱水。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、组织学和功能研究以及血流动力学的机制研究 修改后，这项综合提案旨在从根本上深入了解雌激素对 声带脱水生物学。需要这些数据来推动有关声乐的临床建议 在水合和荷尔蒙状态改变的条件下折叠生理学。