GROWTH FACTORS IN FOLLICULAR DEVELOPMENT

描述：(改编自申请者摘要)使用隔离 长期培养中完整的卵泡提供了一种替代培养的方法 分离出卵泡的细胞成分。这种方法允许进行研究 在更自然的滤泡环境中增殖的细胞。这些 卵泡合成cAMP和类固醇，增殖并对 促性腺激素以及表达促性腺激素受体和独特的蛋白质。 此外，该模型还表明FSH的促有丝分裂作用是中介的。 通过表皮生长因子(EGF)的作用。期间的研究计划 过去4年和未来拟议的拨款重点放在腔前 与有腔卵泡相比，人们对卵泡知之甚少。 研究人员已经证实，仓鼠毛囊细胞表达EGF， 转化生长因子β1和β2、表皮生长因子和转化生长因子β 感受器。本提案的目的是界定S的角色 激素和生长因子对EGF和TGF-β表达的调节 受体及生长因子受体的功能意义 卵泡发育过程中基因表达的调控机制 卵泡发生。工作假说是其中一种机制 生长因子调节的卵泡发育涉及到一个负面的 EGF-R和TbetaR的相互作用，其表达起关键作用 决定因素引导滤泡细胞增殖或 功能分化(例如，雄激素和雌激素的开始 合成)--卵泡发育的两个最基本的要求。 卵泡细胞中生长因子受体的表达反过来又是 受促性腺激素、卵巢类固醇和生长因子的关键调控 他们自己。这一假设将在腔前卵泡和腔前卵泡上进行验证。 暴露于内源性激素的周期性仓鼠，腔前卵泡 在长期去垂体(HX)仓鼠中失去激素支持， 对体外培养的周期仓鼠和HX仓鼠的腔前卵泡 促性腺激素、卵巢类固醇、表皮生长因子和转化生长因子-β的存在： (1)滤泡细胞的免疫组织化学和生化分析 增殖和生长因子受体的表达，(2)分析 卵泡类固醇激素生成；(3)转化生长因子-β的定量RT-PCR分析 受体基因转录本。这些信息将揭示 卵巢内激素调控卵泡发生的机制 增长因素。

DESCRIPTION: (adapted from the applicants abstract) The use of isolated intact follicles in long term culture provides an alternative to culture of isolated cellular components of follicles. This method allows for the study of proliferating cells in their more natural follicular environment. These follicles synthesize cAMP and steroids, proliferate and respond to gonadotropins as well as express gonadotropin receptors and unique proteins. In addition, this model shows that the mitogenic action of FSH is mediated via the action of epidermal growth factor (EGF). The research plan during the past 4 years and in the proposed future grant focuses on preantral follicles about which little is known in comparison to antral follicles. The investigator has established that hamster follicular cells express EGF, transforming growth factors beta (TGF-beta1 and -beta2), EGF and TGF-beta receptors. The goal of the present proposal is to define the role(s) of hormones and growth factors in modulating the expression of EGF and TGF-beta receptors, and the functional implications of growth factor receptor expression during follicular development as a mechanism regulating folliculogenesis. The working hypothesis is that one of the mechanisms of growth factor regulated follicular development involves a negative interaction of EGF-R and TbetaR, the expressions of which act as a pivotal determinant to direct follicular cells either to proliferation or to functional differentiation (e.g., onset of androgen and estrogen synthesis)--two most fundamental requirements for follicular development. Growth factor receptor expressions in follicular cells, in turn, is critically regulated by gonadotropins, ovarian steroids and growth factors themselves. The hypothesis will be tested on preantral and antral follicles exposed to endogenous hormones in cyclic hamsters, on preantral follicles deprived of hormonal support in long term hypophysectomized (HX) hamsters, and on preantral follicles from cyclic and HX hamsters cultured in vitro in the presence of gonadotropins, ovarian steroids, EGF and TGF-beta using: (1) immunohistochemical and biochemical analyses of follicular cell proliferation, and growth factor receptor expression, (2) analysis of follicular steroidogenesis, and (3) quantitative RT-PCR analyses of TGF-beta receptor gene transcripts. The information will shed light on the mechanisms involved in hormonal control of folliculogenesis via intraovarian growth factors.