NATURE OF STEROID-RECEPTOR INTERACTIONS

目的是定义类固醇的初始细胞内事件 荷尔蒙作用。这些事件包括类固醇与细胞内的结合 受体分子，受体-类固醇复合体对 DNA结合和核结合物种，以及被激活的 与参与调节的核受体结合部位的复合体 特定基因的转录。其中一种方法已经被用来 检查这些步骤是比较激动剂和拮抗剂的性质 受体-类固醇复合体。对诱导量的详细研究 两种抗糖皮质激素对大鼠酪氨酸氨基转移酶的影响 肝癌组织培养株(HTC和Fu5-5)显示，每种细胞 抗糖皮质激素在Fu5-5中表现出约2倍的激动剂活性 细胞，而不是HTC细胞。同时，人们注意到， 最大TAT的50%所需的几种糖皮质激素浓度 Fu5-5细胞的诱导(即EC50)比HTC低约6倍 细胞。这两个参数的值随着时间的推移而变化。一次回顾 分析表明，两者之间存在极好的线性、互惠关系 不可逆抗糖皮质激素的激动剂活性 21-甲磺酸地塞米松与糖皮质激素地塞米松的EC50 (r=-0.896[n=46])。TAT酶活性的这些变化与 TAT mRNA序列数量的变化，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 已经记录了糖皮质激素诱导TAT的一种新的调制 成绩单。在基因控制方面，还没有观察到这样的调节 任何其他类固醇激素的转录本，但可能与已知的 体内大多数抗类固醇药物激动剂活性的变化 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.