HORMONAL REGULATION OF ENZYME LEVELS IN MAMMALIAN TISSUE

这项研究的主要目的是确定 激素调节胞浆β-烯醇式丙酮酸基因的表达 大鼠体内的羧酸激酶。这将涉及到进一步的刻画 5‘侧翼序列中包含响应于 CAMP和其他激素以及基因区域的鉴定 参与其组织特异性表达。我们还计划隔离和 确定可能在监管中作为中间体的因素 对P-烯醇式丙酮酸羧激酶基因表达的影响。 我们计划的具体主要目标是： 1.鉴定调控β-烯醇式丙酮酸的序列 CAMP、胰岛素和糖皮质激素对羧酸激酶基因表达的影响。 2.确定激素调节转录的中间产物 用体外转录实验检测P-烯醇式丙酮酸羧酸激酶基因。 3.研究β-烯醇式丙酮酸羧激酶mRNA的成熟和周转。 4.确定负责组织特异性调控的序列 P-烯醇式丙酮酸羧酸激酶基因。 我们的长期目标是扩大我们对荷尔蒙的了解 P-烯醇式丙酮酸羧基激酶基因表达的调控 糖尿病等疾病。我们还计划开发新的程序，用于 在哺乳动物细胞中引入该基因的功能拷贝，以便 研究其对特定组织代谢途径的影响。

The broad aim of this research is to determine the mechanism by which hormones regulate the expression of the gene for cytosolic P-enolpyruvate carboxykinase from the rat. This will involve the further characterization of the 5'-flanking sequences which contain regulatory regions responsive to cAMP and other hormones and the identification of areas of the gene involved in its tissue specific expression. We also plan to isolate and identify factors which may be involved as intermediates in the regulation of P-enolpyruvate carboxykinase gene expression. Specific major goals of our program will be to: 1. Identify sequences responsible for regulation of P-enolpyruvate carboxykinase gene expression by cAMP, insulin and glucocorticoids. 2. Determine intermediates in the hormonal regulation of transcription of the P-enolpyruvate carboxykinase gene using in vitro transcription assays. 3. Study the maturation and turnover of P-enolpyruvate carboxykinase mRNA. 4. Identify sequences responsible for the tissue specific regulation of the P-enolpyruvate carboxykinase gene. Our long term objective is to extend our knowledge of the hormonal regulation of P-enolpyruvate carboxykinase gene expression especially in diseases such as diabetes. We also plan to develop new procedures for introducing functional copies of this gene in mammalian cells in order to study its effect on metabolic pathways in specific tissue.