ROLE OF STRESS IN PCOS: NEURONAL MECHANISMS

压力在多囊卵巢综合症中的作用：神经机制

• 批准号: 8357853
• 负责人: Mary B Zelinski
• 金额: $ 3.63万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357853
• 关键词: 3-Dimensional; Address; Alginates; Antral; Catecholamines; Encapsulated; Fertility; Follicular Fluid; Funding; Grant; Growth; Hormones; Human; Infertility; Macaca; Metabolism; Monkeys; National Center for Research Resources; Nerve Fibers; Neurons; Norepinephrine; Ovarian; Ovary; Patients; Pharmaceutical Preparations; Primates; Principal Investigator; Production; Research; Research Infrastructure; Resources; Role; Somatotropin; Source; Stress; Syndrome; Techniques; United States National Institutes of Health; Woman; base; cost; density; insight; novel; uptake

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Polycystic Ovarian Syndrome (PCOS), the leading cause of infertility in women, is characterized by arrested growth of antral follicles by currently unknown mechanisms. Recent evidence in primate ovaries suggests a role for catecholamines, specifically norepinephrine, also known as a stress hormone, as regulators of follicular growth. The increased density of nerve fibers that release catecholamines observed in PCOS ovaries, as well as evidence for altered levels of catecholamines in follicular fluid from PCOS follicles; provide the rationale to explore these factors in a more direct approach. Importantly, the cellular mechanism responsible for up-take, storage and release of catecholamines are found in both human and monkey follicles, thus creating a follicular microenvironment that could regulate follicular function. In order to directly address the question whether and how catecholamines can impact follicular growth and function, we are using the novel technique of 3-dimensional culture of follicles recently developed in the macaque. Primary and secondary follicles are isolated from macaque ovaries, encapsulated in an alginate matrix and individually cultured with natural catecholamines and drugs which are able to interfere with catecholamine uptake, storage release and metabolism. Follicle survival, growth, hormone production and other functional parameters is being determined. These studies will delineate whether catecholamines are novel regulators of primate follicular growth and function. Emerging insights into the modes of actions of catecholamines in the primate ovary could provide the basis for treatments to normalize follicular growth and function in patients with PCOS, thereby restoring fertility.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 多囊卵巢综合症（PCOS）是女性不孕的主要原因，其特征是窦卵泡的生长受到目前未知的机制抑制。 最近在灵长类动物卵巢中的证据表明儿茶酚胺，特别是去甲肾上腺素（也称为应激激素）作为卵泡生长的调节剂发挥着作用。 在 PCOS 卵巢中观察到释放儿茶酚胺的神经纤维密度增加，以及 PCOS 卵泡中的卵泡液中儿茶酚胺水平发生变化的证据；提供以更直接的方法探索这些因素的基本原理。 重要的是，在人类和猴子的卵泡中都发现了负责吸收、储存和释放儿茶酚胺的细胞机制，从而创造了一个可以调节卵泡功能的卵泡微环境。为了直接解决儿茶酚胺是否以及如何影响卵泡生长和功能的问题，我们正在使用最近在猕猴中开发的卵泡三维培养新技术。从猕猴卵巢中分离出初级和次级卵泡，封装在藻酸盐基质中，并与天然儿茶酚胺和能够干扰儿茶酚胺吸收、储存释放和代谢的药物单独培养。卵泡存活、生长、激素产生和其他功能参数正在确定。 这些研究将阐明儿茶酚胺是否是灵长类动物卵泡生长和功能的新型调节剂。 对儿茶酚胺在灵长类动物卵巢中的作用模式的新见解可以为使多囊卵巢综合症患者的卵泡生长和功能正常化从而恢复生育能力的治疗提供基础。