HORMONE REGULATION--VITELLOGENIN & LIPOPROTEIN SYNTHESI

这项研究涉及卵黄蛋白原的激素调节和 极低密度脂蛋白的载脂蛋白。这些蛋白质是 在禽类肝脏对雌激素刺激的反应和合成 用于将脂肪和其他营养物质输送到卵黄中供胚胎使用 发展。这些蛋白质作为研究的模型非常有兴趣。 雌激素的作用以及它们在脂类运输中的作用。这 提案主要集中在载脂蛋白II(Apo II)的调节上。 基因表达。载脂蛋白II是极低密度脂蛋白的主要蛋白质成分 雌激素作用下合成的密度脂蛋白颗粒。这个 雌激素刺激载脂蛋白II的合成涉及基因的激活 转录和显著的细胞质稳定的载脂蛋白II的mRNA。 将进行实验，以检查雌激素介导的 载脂蛋白II基因的稳定化及其稳定性假设的检验 是由于稳定因子和载脂蛋白之间的特定部位的相互作用 II基因的表达。这项研究将针对三个主要问题。第一, 载脂蛋白II的mRNA结构与其功能方面有何关系？ 表情？这些研究需要阐明这种异质性。 基因5‘端和3’端的发现及载脂蛋白II基因的分析 二级结构。一种新的高分辨率mRNAs作图方法 为此开发了具有碱基和结构的特定核糖核酸酶 目的。第二，什么是蛋白质结合在信使核糖核酸和 它与载脂蛋白II基因的二级结构和稳定性有何关系？ 核酸酶图谱将被用于确定被改变为 与蛋白质相互作用的结果。第三，做载脂蛋白II信使 核糖核蛋白颗粒含有这种核糖核酸所特有的蛋白质？是这样的吗？ 参与雌激素介导的稳定的蛋白质。这些粒子将 进行提纯和蛋白质分析。抗载脂蛋白II的单抗 Mrnp蛋白将用于确定哪些蛋白是载脂蛋白II所特有的。 MRNA，这是雌激素调节的mRNAs共同的，也是 所有的mRNAs。长期目标是了解雌激素是如何介导的 信使核糖核酸发生稳定。这是雌激素的主要作用，它具有 受到的关注相对较少。

This research concerns the hormonal regulation of the vitellogenins and the apolipoproteins of very low density lipoprotein. These proteins are synthesized in the avian liver in response to estrogenic stimulation and serve to transport lipid and other nutrients to the yolk for embryonic development. These proteins are of great interest as models for the study of estrogen action and because of their roles in lipid transport. This proposal is largely focused on the regulation of apolipoprotein II (apo II) gene expression. Apo II is a major protein component of the very low density lipoprotein particles synthesized in response to estrogen. The estrogen-stimulated synthesis of apo II involves activation of gene transcription and a marked cytoplasmic stabilization of apo II mRNA. Experiments will be carried out to examine the estrogen-mediated stabilization of apo II mRNA and to test the hypothesis that stabilization is due to site specific interactions between stabilization factors and apo II mRNA. The research will be directed to three major questions. First, how is apo II mRNA structure related to functional aspects of its expression? These studies will require elucidation of the heterogeneity found at the 5' and 3' ends of the mRNA and an analysis of apo II mRNA secondary structure. A new method for high resolution mapping of mRNAs with base and struture specific ribonucleases has been developed for this purpose. Second, What is the pattern of protein binding on the mRNA and how does it relate to secondary structure and stabiliztion of apo II mRNA? Nuclease mapping will be used to determine sequences that are altered as a result of interaction with protein. Third, do apo II messenger ribonucleoprotein particles contain proteins unique to this mRNA? Are such proteins involved in estrogen-mediated stabilization. These particles will be purified and the proteins analyzed. Monoclonal antibodies to apo II mRNP proteins will be used to determine which proteins are unique to apo II mRNA, which are common to etrogen-regulated mRNAs, and which are common to all mRNAs. The long-term goal is to understand how estrogen-mediated stabilization of mRNA occurs. This is a major action of estrogens that has received relatively little attention.