Hormonal signals that regulate ovarian differentiation

卵泡发育是一个动态的过程，在发育的每个阶段都需要对卵巢中的多种细胞类型进行精细的调节，以应对局部产生的和性腺外的因素。在这次竞争性的项目更新中，我们将把我们在核受体、小鼠模型、卵巢组织病理学、神经内分泌调节和信号转导方面的各种专业知识结合到三个全面和高度互动的项目中，以评估激活素、雌激素和FSH信号调节卵巢卵泡发育的机制。这些因素中的任何一个对正常信号的干扰都会导致 不孕不育或不育。我们将测试以下假设：激活素在卵巢卵泡的正常发育中发挥关键作用，正常的卵泡发育需要通过雌激素受体α传递信号，而不是依赖于它与DNA雌激素反应元件的结合，以及FSH通过蛋白激酶A引导的信号传递，从而磷脂酰肌醇3-激酶途径同时解除抑制颗粒细胞分化和刺激分化的抑制通路。研究项目和支持核心是：项目I，激活素调控卵巢卵泡发育，Kelly Mayo博士和Teresa Woodruff博士；项目II，非经典雌激素受体在卵巢中的阿尔法作用，Larry Jameson博士，Jon Levine和Mary Hunzicker-Dunn博士；项目III，FSH刺激信号调节卵泡成熟，Mary Hunzicker-Dunn博士和Larry Jameson博士；核心A，行政核心Mary Hunzicker-Dunn博士；核心B，卵巢采购、处理和分析核心Teresa Woodruff博士。该方案项目中涉及的问题构成了生育率管制的实质。通过我们的共同努力，我们将优化每个项目的进展，以更好地了解控制卵泡发育的情况。

Ovarian follicle development is a dynamic process that requires exquisite regulation of multiple cell types in the ovary in response to locally produced and extragonadal factors at each stage of development. In this competitive renewal of our Program Project we will combine our various expertise's in nuclear receptors, mouse models, ovarian histopathology, neuroendocrine regulation, and signaling into three comprehensive and highly interactive projects to evaluate the mechanisms by which activin, estrogen, and FSH signal to regulate ovarian follicular development. Interruption of the normal signaling by any of these factors results in infertility or subfertility. We will test the hypotheses that activin plays a critical role in normal development of the ovarian follicles, that normal follicular development requires signaling through estrogen receptor alpha that is not dependent on its binding to DNA estrogen response elements, and that FSH-directed signaling via protein kinase A and consequently the phosphatidylinositol 3-kinase pathway simultaneously disengages an inhibitory pathway that restrains granulosa cell differentiation and stimulates differentiation. The research projects and supporting cores are: Project I, Activin Regulation of Ovarian Follicle Development, Drs. Kelly Mayo and Teresa Woodruff; Project II, Nonclassical Estrogen Receptor Alpha Action in the Ovary, Drs. Larry Jameson, Jon Levine and Mary Hunzicker-Dunn; Project III, FSH-Stimulated Signals that Regulate Follicular Maturation, Drs. Mary Hunzicker-Dunn and Larry Jameson; Core A, Administrative Core, Dr. Mary Hunzicker-Dunn; Core B, Ovarian Procurement, Processing and Analysis Core, Dr. Teresa Woodruff. The issues addressed in the Program Project underlie the essence of the regulation of fertility. By our united efforts we will optimize progress on each project to better understand the control follicular development.