GLUCOCORTICOID ACTION IN SYNCHRONIZED CELLS

我们的研究目标是继续探索这种机制。 糖皮质激素在细胞周期中的作用。在.工作 该实验室和其他实验室已经证实， 细胞在细胞周期中导致显著的变化 糖皮质激素受体的数量和结构。我们现在将集中精力 糖皮质激素受体基因调控的研究 在细胞周期中。猪瘟病毒基因克隆的可得性 人类糖皮质激素受体允许我们扩展我们的分析 从受体调节到分子水平。我们假设 细胞内糖皮质激素受体数量的变化 细胞周期可以通过受体基因的改变来解释 监管。为了解决这个问题，我们将评估 糖皮质激素受体mRNA的积累、转录和 在细胞周期中的稳定性。同时，组织机构 糖皮质激素受体基因的结构将被评估为 确定受体基因之间存在什么关系(如果有) 转录和受体基因结构。进一步的研究将 也被启动以鉴定和表征DNA序列 糖皮质激素受体基因表达所必需的。最后我们 寻求进一步评估最近在我们的 演示人类交互作用的实验室 糖皮质激素受体及其基因的编码域。 具体地说，我们将通过几个标准来描述 糖皮质激素受体与其自身基因的相互作用 在体内评价这类物质的生理学意义 互动。综合申请中提出的研究 应该有助于更好地理解所涉及的机制 在人糖皮质激素受体基因的调控中 表情。

The goal of our research is to continue to explore the mechanisms of glucocorticoid hormone action during the cell cycle. Work in this and other laboratories has established that the progression of cells through the cell cycle results in significant alterations in glucocorticoid receptor number and structure. We will now focus our studies on the regulation of the glucocorticoid receptor gene during the cell cycle. The availability of cDNA clones of the human glucocorticoid receptor permits us to extend our analysis of receptor regulation to the molecular level. We hypothesize that changes in cellular glucocorticoid receptor number during the cell cycle can be accounted for by alteration in receptor gene regulation. To address this question we will evaluate glucocorticoid receptor mRNA accumulation, transcription and stability during the cell cycle. Concurrently the organizational structure of the glucocorticoid receptor gene will be assessed to determine what relationship, if any, exists between receptor gene transcription and receptor gene structure. Further studies will also be initiated to identify and characterize the DNA sequences necessary for glucocorticoid receptor gene expression. Finally we seek to evaluate further a recent observation made in our laboratory which demonstrates the interaction of the human glucocorticoid receptors with the coding domain of its gene. Specifically we will characterize by several criteria the interactions between glucocorticoid receptor and its own gene and evaluate in vivo the physiological significance of such interactions. Together the studies proposed in the application should lead to a better understanding of the mechanisms involved in the regulation of human glucocorticoid receptor gene expression.