AUTOREGULATION OF GLUCOCORTICOID RECEPTOR GENE-EXPRESSION
AUTOREGULATION OF GLUCOCORTICOID RECEPTOR GENE-EXPRESSION
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DOI：
10.1016/0039-128x(91)90124-e
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发表时间：
1991-02-01
期刊：
影响因子：
2.7
通讯作者：
CIDLOWSKI, JA
中科院分区：
文献类型：
--
作者：
BURNSTEIN, KL;BELLINGHAM, DL;CIDLOWSKI, JA
糖皮质激素受体是高度保守的类固醇受体蛋白家族的成员，是依赖配体的转录因子。以往的研究表明，功能性糖皮质激素受体的存在是细胞对激素反应表现的先决条件。糖皮质激素受体在糖皮质激素治疗后发生下调。为了确定参与这一过程的分子机制，我们分析了含有内源性受体的HeLa细胞和含有通过DNA转染引入的受体的细胞中糖皮质激素受体的下调。我们的研究结果表明，含有糖皮质激素受体的细胞——无论是内源性的还是转染的——都以非常相似的方式经历了类固醇结合能力的下调，以及受体蛋白和mRNA水平的降低。人类糖皮质激素受体cDNA编码区的DNA序列似乎足以解释受体的下调。这一新发现提示糖皮质激素受体稳态的控制具有独特的机制。
Glucocorticoid receptors are members of a highly conserved family of steroid receptor proteins, which are ligand-dependent transcription factors. Previous studies have shown that the presence of functional glucocorticoid receptors is a prerequisite for manifestation of cellular responses to hormone. Glucocorticoid receptors undergo down-regulation following treatment with glucocorticoids. To define the molecular mechanisms that are involved in this process we have analyzed the down-regulation of glucocorticoid receptors both in HeLa cells, which contain endogenous receptors, and in cells containing receptors that have been introduced by DNA transfection. Our results show that cells that contain contain glucocorticoid receptors-either endogenous or transfected-undergo down-regulation of steroid-binding capabilities, as well as reductions in receptor protein and mRNA levels, in a remarkably similar fashion. DNA sequences in the coding region of the human glucocorticoid receptor cDNA appear to be sufficient to account for down-regulation of receptor. This novel finding suggests that unique mechanisms are involved in controlling glucocorticoid receptor homeostasis.