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

项目摘要/摘要 性激素对声带(VF)的健康至关重要；然而，性激素和性激素的个体效应 VFS上的激素受体知之甚少。这种知识上的鸿沟是由两个 VFS的一般不可达性以及荷尔蒙和声音之间的复杂关系 混杂因素在人声文学中的混杂。因此，更好地理解荷尔蒙如何影响 喉的潜在机制和发声功能是预防和治疗的关键。 荷尔蒙相关的嗓音障碍。因此，这项研究的主要目标是首先量化性别 VFS中的激素受体(Aim 1)，然后量化VF生物学(Aim 2a)和发声声学的变化 (目标2b)每种主要性激素(睾酮、雌二醇和孕酮)及其相应的 荷尔蒙受体。使用大鼠模型，我们将检验中枢假说，即受体在体内的分布 雄性大鼠和雌性大鼠的VFS将有所不同(目标1)。在性腺切除的大鼠中，选择性激活激素 睾酮(男性)、雌二醇(女性)和黄体酮(女性)受体的结构将发生变化。 和功能(目标2a)，并将导致发声的改变 声学(目标2b)。通过定义个体荷尔蒙对室颤健康和发声行为的贡献，这项研究 将为荷尔蒙相关发声障碍的预防和逆转提供科学指导。这项工作是 创新归功于专门的方法，将1)量化VFS中的激素受体和2) 选择性激活特定激素受体以区分初级性激素的个体贡献 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 荷尔蒙对声学的特定影响对于理解哪些治疗策略可能 可归因于性激素丧失的发声功能改变。该培训计划将为您提供 PI成为独立翻译代言人所需的时间、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以及2) 向威斯康星大学麦迪逊分校唯一合格的导师学习。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之前评估的研究的基础上 荷尔蒙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 他们关于发声障碍的理论框架，提炼了他们的科学写作和传播，并为他们的 有能力继续进行可资助的、持久的、有计划的研究，这将有助于 传播学和精神障碍。这一语音研究的翻译路线对于推动 语言病理学的一门学科，通过消除激素及其受体对语言的影响的歧义 发声机制，允许更知情的评估，治疗和预防发声障碍。

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.