OVARIAN GROWTH FACTORS

描述（改编自研究者摘要）：本提案旨在 为了更全面地了解卵巢IGF系统， 通过深入了解三个关键组成部分，IGF-1， IGFBP-2和IGFBP-3及其相互作用。 中央调查目标 关于IGF-1是激素控制其生物合成在卵巢 细胞 这些研究将建立FSH、CAMP的作用机制 和生长激素，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基因启动子中的激素应答序列的定位和 成熟肽的培养。 将确定IGFBP-2和-3的作用 通过检测它们与卵巢靶细胞的相互作用以及它们的作用， 一系列卵巢特异性细胞功能。 的正确性 这些体外研究产生的假设将在 携带敲除或扩增转基因的转基因小鼠， 这些关键要素的表达。 这些结果可能具有重要意义。 对人类疾病过程的影响。 试图操纵 IGF系统在不孕症患者中已经被引入 诊所。 来自人体体外和组织化学研究的数据 这一系统在疾病过程中的扭曲， 多囊卵巢综合症 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.