Hormonal signals that regulate ovarian differentiation

卵巢卵泡发育是一个动态的过程，需要卵巢内多种细胞类型的精细调节，以响应每个发育阶段局部产生的和卵泡外的因素。在这个竞争性更新的项目中，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传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都会导致正常信号的中断

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.