OVARIAN GROWTH FACTORS

描述(改编自《调查员摘要》)：本提案寻求 为了建立一个更完整和完整的卵巢IGF系统 通过加深对三个关键组成部分的了解，IGF-1， IGFBP-2和IGFBP-3及其相互作用。中央侦查目标 关于IGF-1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 和生长激素，是该基因的主要刺激物，在质量和 IGF-1基因转录的定量方面。这些研究将需要 胰岛素样生长因子-1基因启动子中激素反应序列的定位 培养中的成熟多肽。将确定IGFBP-2和-3的作用 通过研究它们与卵巢靶细胞的相互作用及其影响 卵巢的一系列特殊细胞功能。最后，验证了该规则的有效性。 从这些体外研究中产生的假说将在 携带转基因小鼠的转基因小鼠可以敲除或扩增 这些关键组件的表达。这些结果可能具有重要的意义 对人类疾病过程的影响。试图操纵 胰岛素样生长因子系统在不孕症患者中的应用 诊所。来自人体体外和组织化学研究的数据 该系统在疾病过程中的牵连扭曲，例如 多囊卵巢综合征。我们自己的研究表明， 用于人类的动物模型。

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.