Bourgeois S, Pfahl M, Baulieu E E
EMBO J. 1984 Apr;3(4):751-5. doi: 10.1002/j.1460-2075.1984.tb01879.x.
RU-486 is an anti-fertility steroid which also has anti-glucocorticosteroid effects. RU-486 is shown to be a strong antagonist of the glucocorticosteroid-induced cytolytic response of the murine thymoma lines W7TB and T1M1b , and of the induction of mouse mammary tumor virus (MMTV) mRNA in T1M1b cells. The glucocorticosteroid receptor of W7 cells has high affinity for RU-486 (Kd = 3 X 10(-9) M) but the complex formed has low nuclear transfer capacity. Binding of RU-486, as compared with the glucocorticosteroid agonist triamcinolone acetonide, to mouse receptor results in a decreased affinity for DNA in general and a reduced specific recognition of a site in the promoter region of MMTV proviral DNA. The RU-486 complex formed with rat liver receptor exhibits the same behavior; in addition, it is shown that only a fraction of these complexes are activated by temperature and these form highly salt-sensitive interactions with DNA. These results indicate that the binding of RU-486 to glucocorticosteroid receptors mimics pharmacologically the properties of a class of receptor variants (nt-) which are non-functional and have reduced nuclear transfer and altered DNA binding capacity. These results substantiate the importance of DNA binding in receptor function.
RU - 486是一种抗生育甾体，同时也具有抗糖皮质激素的作用。RU - 486被证明是糖皮质激素诱导的小鼠胸腺瘤细胞系W7TB和T1M1b细胞溶解反应以及T1M1b细胞中鼠乳腺肿瘤病毒（MMTV）mRNA诱导的强拮抗剂。W7细胞的糖皮质激素受体对RU - 486具有高亲和力（Kd = 3×10^(-9) M），但形成的复合物具有低核转运能力。与糖皮质激素激动剂曲安奈德相比，RU - 486与小鼠受体的结合总体上导致对DNA的亲和力降低，以及对MMTV前病毒DNA启动子区域中一个位点的特异性识别减少。与大鼠肝脏受体形成的RU - 486复合物表现出相同的行为；此外，研究表明这些复合物中只有一部分会被温度激活，并且它们与DNA形成高度盐敏感的相互作用。这些结果表明，RU - 486与糖皮质激素受体的结合在药理学上模拟了一类无功能的受体变体（nt -）的特性，这类变体具有降低的核转运能力和改变的DNA结合能力。这些结果证实了DNA结合在受体功能中的重要性。
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