Estrogenic regulation of systemic vocal fold dehydration

全身声带脱水的雌激素调节

• 批准号: 10595038
• 负责人: Abigail Cox
• 金额: $ 63.74万
• 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/10595038
• 关键词: Acoustics; Address; Adult; Affect; Air Movements; Animal Model; Animals; Automobile Driving; Behavioral; Biological; Biology; Biomechanics; 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.

项目摘要 雌激素的核心作用是调节体内的水合平衡。体内（全身）水合减少， 导致全身性声折叠脱水。全身性声折叠脱水改变了组织的生物学。 然而，雌激素在调节这些全身声折的这些生物学变化方面的重要性 脱水仍然未知。我们通过研究了这个重要的临床和理论问题 在研究设计中，转录组，蛋白质组，组织形态和超声发声结果 仔细操纵激素状态和水合状态。我们还将检查雌激素对 全身脱水与改变的相互作用后，血管几何形状和血液流向喉部 激素状态。我们将大鼠动物模型用于这些研究，因为该模型可以实现鲁棒和严格 控制水合和荷尔蒙水平。因为雌激素是重要的，无论生物学性别如何 将包括雄性和雌性大鼠。为了检查激素损失和替代的影响，我们将 当通过手术去除生殖器官时测量结果（卵形切除和 当将雌激素替代用雌二醇替代时。系统性脱水将是 由水限制的翻译范式诱导5天。自由进入水的动物将服务 作为脱水的控制。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 关于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差异化，并且 肌肉和这些组织层具有独特的细胞组织和生物力学特性，声带折叠 分别检查粘膜和肌肉。我们的第二个目标是研究荷尔蒙的相互作用 超声发声的状态和脱水。我们的第三个目标是检查荷尔蒙的影响 这些变化的血管几何形状，血流和生理后果的状态和脱水。 通过结合分子，组织学和功能研究以及血流动力学的机理研究 修改，这项全面的提议旨在使雌激素对雌激素的影响的基本见解 声带脱水生物学。需要这些数据来推动与人声有关的临床建议 在水合和激素状态改变的条件下，折叠生理学。