OVARIAN IGFS: ENDOCRINE VS PARACRINE EFFECTS

卵巢 IGFS：内分泌与旁分泌的影响

• 批准号: 2673809
• 负责人: JAMES M HAMMOND
• 金额: $ 24.9万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-05 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2673809
• 关键词: animal tissue; autocrine; binding proteins; blocking antibody; chemical binding; female; gene expression; graafian follicles; histochemistry /cytochemistry; hormone regulation /control mechanism; immunocytochemistry; in situ hybridization; insulinlike growth factor; menstrual cycle; microcirculation; ovary; paracrine; perfusion; protein isoforms; protein transport; reproductive system circulation; steroid biosynthesis; swine

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.

该建议旨在确定内分泌的相对意义， IGF系统的自分泌和旁分泌成分 体内猪卵巢。它建立在数年的工作基础上 强调定义分泌和分泌的体内技术 卵巢IGF及其结合蛋白（IGFBP）的作用。这些 数据导致推定该增长因子的关键作用 卵巢功能的系统 - 将在 当前的建议。为了解决这些问题，我们将首先确定 IGF和生物合成，定位和结合的卵巢遗迹 它们在生殖周期中的BPS。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 控制本地生产和循环IGF的分布 卵巢。 接下来，我们将确定循环IGF的访问 通过一系列体内的卵巢的几个功能成分 灌注研究。我们希望发现流通的IGF可以访问 她以选择性和有针对性的方式对她的卵巢进行统治 通过IGFBP进行测量。最后，我们将评估生理影响 灌注的IGF及其在类固醇生成和卵泡上的BPS 发展;此外，我们将通过探测来阻止卵巢IGF效应 带有抗IGF-I抗体的体内卵巢。在总体中，这些 研究将提供有关重要性的基本缺失信息 IGF及其BPS在卵巢生理学中的功能；现在 这些功能只能从培养或体内的研究中推测 相关性。这些结果应该对 人类的疾病过程。尝试操纵IGF系统 患者已经被引入 - 不孕诊所。来自 人类的体外和组织化学研究已暗示扭曲 该系统在疾病过程中，例如多囊卵巢 综合征。