OVARIAN IGFS: ENDOCRINE VS PARACRINE EFFECTS

这项建议旨在确定内分泌的相对重要性， 胰岛素样生长因子系统的自分泌、旁分泌成分的功能 活体内的猪卵巢。它建立在几年的工作基础上 强调体内技术，它定义了分泌和 卵巢IGF及其结合蛋白(IGFBPs)的作用这些 数据导致了这种增长因素的关键作用的推定 卵巢功能的系统--这一假说将在 目前的建议。为了解决这些问题，我们将首先确定 IGFS和IGFS的生物合成、定位和结合的卵巢部位 它们在生殖周期中的最低血压。这些组织化学研究是 预计将揭示一个细胞外靶向网络，在该网络中IGFBPs 管理当地生产和流通的IGF在 卵巢。接下来，我们将确定循环IGF对 卵巢的几个功能成分通过体内的一系列 血流灌注研究。我们希望发现循环中的IGF可以访问 以选择性和针对性的方式进入她的卵巢，在大范围内进行治理 由IGFBP进行测量。最后，我们将评估生理效应 胰岛素样生长因子及其对类固醇激素生成和卵泡的影响 此外，我们还将通过灌流来阻断卵巢IGF的影响。 体内有IGF-I抗体的卵巢。总体而言，这些 研究将提供有关重要性的基本缺失信息 以及IGF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出来。 关联性。这些结果应该对以下方面产生重大影响 人类的疾病过程。试图操纵IGF系统 患者已经被介绍到不孕不育诊所。数据来自 在人体内进行的体外和组织化学研究表明， 该系统在多囊卵巢等疾病过程中的作用 综合症。

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.