OVARIAN GROWTH FACTORS

卵巢生长因子

• 批准号: 2609072
• 负责人: JAMES M HAMMOND
• 金额: $ 29.39万
• 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: 1996-12-01 至 2000-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2609072
• 关键词: DNA footprinting; animal tissue; cell proliferation; follicle stimulating hormone; gel mobility shift assay; gene expression; gene targeting; genetic transcription; genetically modified animals; graafian follicles; granulosa cell; growth /development; high performance liquid chromatography; hormone regulation /control mechanism; in situ hybridization; insulinlike growth factor; laboratory mouse; ovary; polymerase chain reaction; protein biosynthesis; somatotropin; tissue /cell culture; transfection; western blottings

DESCRIPTION (Adapted from the Investigator's Abstract): This proposal seeks to develop a more complete and integrated picture of the ovarian IGF system by developing a deeper understanding of three key components, IGF-1, IGFBP-2, and IGFBP-3 and their interaction. Central investigative targets regarding IGF-1 are the hormonal control of its biosynthesis in ovarian cells. These studies will establish the mechanism of action of FSH, CAMP and GH, the principal stimulators of this gene, in terms of qualitative and quantitative aspects of IGF-1 gene transcription. These studies will entail mapping of hormone responsive sequences in the IGF-1 gene promoter and the mature peptide in culture. The action of IGFBP-2 and -3 will be established by examining their interactions with ovarian target cells and their effects on a series of ovary specific cell functions. Finally, the validity of hypotheses generated from these in vitro studies will be tested in transgenic mice bearing transgenes which either knockout or amplify the expression of these key components. These results may have significant implications for disease processes in humans. Attempts to manipulate the IGF system in patients have already been introduced into infertility clinics. Data from in vitro and histochemical studies in humans have implicated distortions of this system in disease processes such as polycystic ovary syndrome. Our own studies suggest many similarities of the animal models used to humans.

描述（改编自研究者的摘要）：该提案寻求 建立更完整、更综合的卵巢 IGF 系统图 通过更深入地了解三个关键成分 IGF-1， IGFBP-2 和 IGFBP-3 及其相互作用。 中央调查对象 关于IGF-1，其在卵巢中生物合成的激素控制 细胞。 这些研究将建立 FSH、CAMP 的作用机制 GH，该基因的主要刺激物，在定性和 IGF-1 基因转录的定量方面。 这些研究将需要 IGF-1 基因启动子和激素响应序列的定位 培养物中的成熟肽。 IGFBP-2和-3的作用将被建立 通过检查它们与卵巢靶细胞的相互作用及其影响 一系列卵巢特异性细胞功能。 最后，有效性 这些体外研究产生的假设将在 带有基因敲除或扩增的转基因小鼠 这些关键成分的表达。 这些结果可能具有重大意义 对人类疾病过程的影响。 试图操纵 IGF系统已被引入不孕不育患者 诊所。 来自人类体外和组织化学研究的数据 该系统在疾病过程中的扭曲，例如 多囊卵巢综合症。 我们自己的研究表明，两者有许多相似之处 用于人类的动物模型。