Hormonal signals that regulate ovarian differentiation

卵巢卵泡发育是一个动态的过程，需要对卵巢中的多种细胞类型进行精细调节，以响应在发育的每个阶段局部产生的和性腺外的因素。在我们的计划项目的竞争性更新中，我们将联合收割机结合我们在核受体，小鼠模型，卵巢组织病理学，神经内分泌调节和信号传导方面的各种专业知识，形成三个全面和高度互动的项目，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种干扰正常信号传导都会导致 不育或生育力低下。我们将测试激活素在卵泡正常发育中起关键作用的假设，正常卵泡发育需要通过雌激素受体α进行信号传导，而雌激素受体α不依赖于其与DNA雌激素反应元件的结合，以及通过蛋白激酶A的FSH引导的信号传导，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途径。研究项目和支持核心是：项目I，卵巢卵泡发育的激活素调节，Kelly马约和Teresa Woodruff博士;项目II，卵巢中的非经典雌激素受体α作用，Larry Jameson，Jon Levine和玛丽Hunzicker-Dunn博士;项目III，调节卵泡成熟的FSH刺激信号，玛丽Hunzicker-Dunn和Larry Jameson博士;核心A，行政核心，玛丽亨齐克邓恩博士;核心B，卵巢采购，处理和分析核心，特蕾莎伍德拉夫博士。该方案项目所处理的问题是生育率调节的实质。通过我们的共同努力，我们将优化每个项目的进度，以更好地了解控制卵泡发育。

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.