NATURE OF STEROID-RECEPTOR INTERACTIONS

目的是确定类固醇激素的初始细胞内事件， 激素作用。 这些事件包括类固醇结合到细胞内 受体分子，“激活”受体-类固醇复合物， DNA结合和核结合物质，以及活化的 复杂的那些核受体位点参与调节 特定基因的转录。 一种被用来 检查这些步骤是为了比较激动剂和拮抗剂的性质 受体类固醇复合物 详细研究了诱导量， 几种抗糖皮质激素对两种大鼠酪氨酸氨基转移酶（达特）影响 肝癌组织培养系（HTC和Fu 5 -5）显示， 在Fu 5 -5中，抗糖皮质激素显示约2倍的激动剂活性 比HTC细胞。 与此同时，有人指出， 50%最大达特所需的几种糖皮质激素浓度 感应（即，EC_（50）比HTC低约6倍 细胞 这两个参数的值随时间变化。 回顾性 分析显示，在这些因素之间存在良好的线性、相互关系。 不可逆抗糖皮质激素激动剂活性量 地塞米松21-甲磺酸盐和糖皮质激素地塞米松的EC 50 （R=-0.896[n=46]）。 达特酶活性的这些变化被 达特mRNA序列的量的变化，但没有观察到 另一种糖皮质激素诱导酶谷氨酰胺合成酶。 因此我们 已经证明了糖皮质激素诱导达特的一种新的调节 成绩单 这种调节尚未观察到的控制基因 任何其他类固醇激素的转录，但可能与已知的 大多数抗类固醇药物在体内的激动剂活性变化， 不同的系统。

The object is to define the initial, intracellular events of steroid hormone action. These events include steroid binding to the intracellular receptor molecule, "activation" of the receptor-steroid complex to a DNA-binding and nuclear-binding species, and binding of the activated complex to those nuclear acceptor sites involved in the regulation of transcription of specific genes. One approach that has been used to examine these steps is to compare the properties of agonist and antagonist receptor-steroid complexes. Detailed studies of the amount of induction of tyrosine aminotransferase (TAT) by several antiglucocorticoids in two rat hepatoma tissue culture lines (HTC and Fu5-5) revealed that each antiglucocorticoid displayed about 2-fold more agonist activity in Fu5-5 cells than in HTC cells. At the same time, it was noted that the concentration of several glucocorticoids required for 50% of maximal TAT induction (i.e., EC50) in Fu5-5 cells were about 6-fold lower than in HTC cells. The values of both parameters varied over time. A retrospective analysis revealed an excellent linear, reciprocal relationship between the amount of agonist activity for the irreversible antiglucocorticoid dexamethasone 21-mesylate and the EC50 of the glucocorticoid dexamethasone (R=-0.896[n=46]). These changes in TAT enzyme activity were paralleled by changes in the amount of TAT mRNA sequences but were not observed with another glucocorticoid inducible enzyme, glutamine synthetase. Thus we have documented a novel modulation of glucocorticoid induction of TAT transcripts. Such modulation has not been observed for the control of gene transcripts by any other steroid hormones but may be related to the known variation in agonist activity seen for most antisteroids in vivo in different systems.