OVARIAN IGFS: ENDOCRINE VS PARACRINE EFFECTS

这项建议旨在确定内分泌的相对重要性， 自分泌和旁分泌成分的IGF系统的功能 猪卵巢的组织结构。它建立在几年的工作基础上 强调已经定义分泌的体内技术， 卵巢IGFs及其结合蛋白（IGFBPs）的作用。这些 数据导致的一个关键作用，这一增长因素的推定 卵巢功能的系统-一个假设，这将在测试 目前的提案。为了解决这些问题，我们将首先确定 IGFs的生物合成、定位和结合的卵巢位点， 在生殖周期中的血压。这些组织化学研究是 预计将揭示一个细胞外靶向网络，其中IGFBPs 管理当地生产和流通的IGFs的分布 卵巢 接下来，我们将确定循环IGFs对 通过一系列的体内实验， 灌注研究。我们希望发现，循环IGFs有机会 以选择性和有针对性的方式切除卵巢， 用IGFBPs来衡量。最后，我们将评估 灌注IGFs及其BP对类固醇生成和卵泡发育的影响 发育;此外，我们将通过灌流阻断卵巢IGF的作用， 卵巢在体内与IGF-I的抗体。总的来说，这些 研究将提供有关重要性的基本缺失信息， IGFs及其BPs在卵巢生理中的作用;目前 这些功能只能从培养或体内研究中推测 相关性这些结果应该对以下方面具有重要意义： 人类的疾病过程。试图操纵IGF系统， 病人已经被介绍到不孕症诊所。数据从 在人体的体外和组织化学研究中， 在疾病过程中，如多囊卵巢， 综合征

This proposal seeks to determine the relative significance of endocrine, autocrine, and paracrine components of the IGF system for the function of the porcine ovary in vivo. It builds on several years of work emphasizing in vivo techniques which have defined the secretion and action of the ovarian IGFs and their binding proteins (IGFBPs). These data lead to the presumption of a critical role for this growth factor system in ovarian function-a hypothesis which will be tested in the current proposal. To address these issues, we will first determine the ovarian sites of biosynthesis, localization, and binding of IGFs and their BPs during the reproductive cycle. These histochemical studies are expected to reveal an extracellular targeting network in which the IGFBPs govern the distribution of locally produced and circulating IGFs within the ovary. Next we will determine the access of circulating IGFs to the several functional components of the ovary through a series of in vivo perfusion studies. We expect to find that circulating IGFs have access to she ovary in a selective and targeted fashion, governed in large measure by the IGFBPs. Finally, we will assess the physiological effects of perfused IGFs and their BPs on steroidogenesis and follicular development; in addition, we will block ovarian IGF effects by perifusing the ovary in vivo with antibodies to IGF-I. In the aggregate, these studies will provide essential missing information about the importance and function of the IGFs and their BPs in ovarian physiology; at present these functions can only be presumed from studies in culture or in vivo correlations. These results should have significant implications for disease processes in humans. Attempts to manipulate the IGF system in patients have already been introduced -to infertility clinics. Data from in vitro and histochemical studies in humans have implicated distortions of this system in disease processes such as the polycystic ovary syndrome.