OVARIAN GROWTH FACTORS

卵巢生长因子

• 批准号: 2901793
• 负责人: JAMES M HAMMOND
• 金额: $ 6.29万
• 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/2901793
• 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（改编自调查员的摘要）：该提案寻求 开发卵巢IGF系统的更完整和整合的图片 通过对三个关键组成部分IGF-1的更深入了解， IGFBP-2和IGFBP-3及其相互作用。 中央调查目标 关于IGF-1是其卵巢生物合成的激素对照 细胞。 这些研究将确定FSH，CAMP的作用机理 GH，该基因的主要刺激剂，就定性和 IGF-1基因转录的定量方面。 这些研究将需要 IGF-1基因启动子和激素反应序列的映射 培养中成熟的肽。 IGFBP -2和-3的作用将建立 通过检查其与卵巢靶细胞的相互作用及其影响 在一系列卵巢特异性细胞功能上。 最后，有效性 这些体外研究产生的假设将在 带有转基因的转基因小鼠敲除或放大 这些关键成分的表达。 这些结果可能具有重要的 对人类疾病过程的影响。 试图操纵 患者的IGF系统已经引入不育 诊所。 来自人类体外和组织化学研究的数据具有 在疾病过程中，该系统牵涉到该系统的扭曲 多囊卵巢综合征。 我们自己的研究表明了许多相似之处 动物模型曾经是人类的。