HORMONAL REGULATION OF ANGIOTENSINOGEN GENE

我实验室的长期目标是 血压调节和血液流动的机制。 现在 变得明显的是，组织特异性系统发挥了 对血压的调节有巨大的影响， 在高血压的发生中起主要作用。 我们重点 血管紧张素原（angen），在循环肾素中很重要 血管紧张素系统，但也在肝外组织合成。 很可能当地一代的angen可以有深刻的 在没有变化的情况下， 循环血管 对血管生成素表达的调控和血管生成素的合成 本地发电系统的功能将有望阐明 所描述的实验。 我们的目标是确定函数 当地的安根一代。 CNS的功能意义 将通过详细的解剖定位（在 原位杂交和穿刺活检研究）与 当归的生理药理调节作用研究 mRNA水平（定量原位杂交和狭缝印迹杂交）。 angen在肾功能中的可能作用将通过以下方法确定： 详细的解剖定位（原位杂交）和研究 通过相关的生理操作来调节angen mRNA。 Angen可能具有重要的自分泌或旁分泌影响， 血管功能 细胞来源的确定 （内皮与平滑肌）将通过原位 杂交方法 监管将通过定量研究， 为大脑开发的原位方法。 我们的目标是确定 使用细胞培养系统调节angen基因。 我们将 表征激素调节（狭缝印迹和核电泳） 关闭）的激素和生长因子在MA10 Leydig细胞和 将结果与在大肠杆菌H35细胞中获得的结果进行比较。 分离和表征的侧翼序列的 angen基因是高水平理解组织所必需的 特异性调控，因此我们将克隆编码大鼠 angen。 然后我们将确定特定的基因组序列 并表征细胞特异性核因子所必需的 for angen angen基因regulation调控. 我们将使用CAT分析和凝胶 获得细胞特异性结合信息的保留法 因子和调控序列。 最后，我们的目标是确定 生长因子在血管生成中的作用。 实体瘤 以及发育中的组织需要足够的血液流动， 血管化以继续生长。 由于血管生成（生长） 现在已经确定了这些因素，我们的目标是确定 这些因素在angen基因的调节。 当安根 基因表达的特征如上所述， 来推断当地一代 影响正常功能或引起病理效应。

The long term goal of my laboratory is to characterize the basic mechanisms of blood pressure regulation and blood flow. It is now becoming apparent that tissue specific systems exert a tremendous influence on the regulation of blood pressure and may play a major role in the genesis of hypertension. We have focused on angiotensinogen (angen), important in the circulating renin angiotensin system, but also synthesized in extra-hepatic tissues. It is likely that local generation of angen can have profound physiologic and pathologic effects in the absence of changes in circulating angen. The control of angen expression and the function of local generating systems will hopefully be elucidated by the experiments described. We aim to determine the function of local angen generation. The functional significance of CNS generation will be elucidated by detailed anatomic localization (in situ hybridization and punch biopsy studies) in combination with studies on the physiologic and pharmacologic regulation of angen mRNA levels (quantitative in situ and slot blot hybridization). The possible roles of angen in renal function will be determined by detailed anatomic localization (in situ hybridization) and studies of angen mRNA regulation by relevant physiologic manipulations. Angen may have important autocrine or paracrine influence on blood vessel function. Determination of the cellular origin (endothelium vs. smooth muscle) will be accomplished by in situ hybridization. Regulation will be studied by the quantitative in situ methods developed for brain. We aim to determine the regulation of angen gene using cell culture systems. We will characterize the hormonal regulation (slot blot and nuclear run off) by hormones and growth factors in MA10 Leydig cells and compare the results to those obtained in Reuber H35 cells. Isolation and characterization of the flanking sequences of the angen gene is required for a high level of understanding of tissue specific regulation, thus we will clone the gene encoding rat angen. We then will determine the specific genomic sequences and characterize the cellular specific nuclear factors necessary for angen gene regulation. We will use CAT assays and the gel retention method to gain information about cell specific binding factors and regulatory sequences. Finally we aim to determine the role of growth factors in angen production. Solid tumors as well as developing tissues need adequate blood flow and vascularization for continued growth. Since angiogenesis (growth) factors have now been identified, we aim to determine the role of these factors in the regulation of the angen gene. When angen gene expression is characterized as above, it will become possible to make inferences about the extent to which local generation effects normal function or causes pathologic effects.