Effects of Primary Sex Hormones and Hormone Receptors on the Vocal Mechanism

项目总结/摘要 性激素对声带（VF）的健康至关重要;然而，性激素的个体效应及其 对VF上的激素受体知之甚少。这种知识上的差距是由两个 一般难以接近的VF以及激素和声音之间的复杂关系， 在人声文献中被混杂的因素所混淆。因此，更好地了解激素如何影响 潜在的喉机制和发声功能对于预防和治疗 与听力有关的声音障碍。因此，这项研究的主要目标是首先量化性别 VF中的激素受体（目标1），然后量化VF生物学（目标2a）和声音声学的变化 (Aim 2b）对于每种主要的性激素（睾酮、雌二醇和孕酮）及其相应的 激素受体使用大鼠模型，我们将测试中心假设，即受体的分布， 雄性大鼠与雌性大鼠的VF不同（目的1）。在性腺切除大鼠中，选择性激活激素 睾酮（男性）、雌二醇（女性）和孕酮（女性）的受体将显示结构变化 和功能的VF粘膜和甲杓肌（目的2a），并将导致改变发声 声学（目标2b）。通过定义个体激素对VF健康和发声行为的贡献， 将为预防和逆转与发音相关的嗓音障碍提供科学指导。这项工作是 创新，由于专门的方法，将1）量化的激素受体在VF和2） 选择性激活特定的激素受体，以区分主要性激素的个体贡献 以及它们的激素受体对VF生物学和声学行为的影响。这项工作意义重大，因为知识 对于理解哪些治疗策略可以 逆转由于性激素丧失而引起的发声功能变化。该培训计划将提供 PI成为独立翻译声音所需的时间、工具、环境和指导 研究员培训活动将利用：1）使用专门资源和设备; 2） 从威斯康星大学麦迪逊分校的合格导师那里学习。这些 经验将为PI提供量身定制的培训，这些培训将建立在他们以前的研究基础上， 激素如何影响喉内肌和声学，最大限度地提高他们的方法技能，扩展 他们的声音障碍的理论框架，完善他们的科学写作和传播，并支架他们的 有能力继续一个可资助的，持久的，有计划的研究路线，这将有助于学科 沟通科学和疾病。这条语音研究的翻译路线对于推进 通过消除激素及其受体对语言的影响， 发声机制允许更知情的评估，治疗和预防声音障碍。

Project Summary/Abstract Sex hormones are critical to vocal fold (VF) health; however, the individual effects of sex hormones and their hormone receptors on the VFs are poorly understood. This gap in knowledge is perpetuated by both the general inaccessibility of the VFs as well as the complex relationship between hormones and the voice that is muddied in the human voice literature by confounding factors. Thus, better understanding how hormones affect the underlying laryngeal mechanism and consequently vocal functions is critical to preventing and treating hormone-related voice disorders. Therefore, primary objectives of this research are to first quantify sex hormone receptors in the VFs (Aim 1) and then quantify changes to VF biology (Aim 2a) and vocal acoustics (Aim 2b) for each primary sex hormone (testosterone, estradiol, and progesterone) and their corresponding hormone receptors. Using a rat model, we will test the central hypotheses that the distribution of receptors in the VFs will be different in male vs. female rats (Aim 1). In gonadectomized rats, selectively activating hormone receptors for testosterone (male), estradiol (female), and progesterone (female) will show changes in structure and function in the VF mucosa and thyroarytenoid muscles (Aim 2a) and will lead to changes in vocal acoustics (Aim 2b). By defining individual hormone contributions to VF health and vocal behavior, this research will provide scientific direction for the prevention and reversal of hormone-related voice disorders. This work is innovative due to the specialized methodology that will 1) quantify hormone receptors in the VFs and 2) selectively activate specific hormone receptors to differentiate individual contributions of primary sex hormones and their hormone receptors on VF biology and acoustic behavior. This work is significant because knowledge of hormone-specific effects on vocal acoustics is critical to understanding which therapeutic strategies may reverse vocal function changes attributable to the loss of sex hormones. This training program will provide the time, tools, environment, and mentorship necessary for the PI to become an independent translational voice researcher. Training activities will capitalize on 1) using the specialized resources and equipment and 2) learning from the uniquely-qualified mentors available at the University of Wisconsin-Madison. These experiences will provide the PI with tailored training that will build on their previous research that evaluated how hormones affect intrinsic laryngeal muscles and acoustics, maximize their methodological skillset, expand their theoretical framework of voice disorders, refine their scientific writing and dissemination, and scaffold their ability to continue a fundable, durable, programmatic line of research that will contribute to the discipline of communication sciences and disorders. This translational line of voice research is important to advance the discipline of speech-language pathology by disambiguating the effects of hormones and their receptors on the vocal mechanism allowing for more informed evaluation, treatment, and prevention of voice disorders.