Differential effect of glucocorticoid receptor antagonists on glucocorticoid receptor nuclear translocation and DNA binding
Differential effect of glucocorticoid receptor antagonists on glucocorticoid receptor nuclear translocation and DNA binding
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糖皮质激素受体拮抗剂对糖皮质激素受体核转位和 DNA 结合的差异作用
DOI：
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发表时间：
2011
影响因子：
4.1
通讯作者：
S. Lightman
中科院分区：
文献类型：
--
作者：
F. Spiga;D. Knight;S. Droste;B. Conway;Y. Kershaw;C. MacSweeney;F. Thomson;M. Craighead;B. Peeters;S. Lightman
本文研究了RU 486和Schering-Plough公司的糖皮质激素受体拮抗剂S-P对糖皮质激素受体核转位和DNA结合的影响。在体外研究中，AtT 20细胞用媒介物或用RU 486、S-P或皮质酮（3-300 nM）处理，或用媒介物或糖皮质激素受体拮抗剂（3-300 nM）和30 nM皮质酮共处理。两种糖皮质激素受体拮抗剂均诱导糖皮质激素受体核转位，但只有RU 486诱导DNA结合。RU 486可增强皮质酮对糖皮质激素受体核转位和DNA结合的影响，S-P可抑制皮质酮诱导的糖皮质激素受体核转位，但对糖皮质激素受体-DNA结合无影响。在体内研究中，肾上腺切除的大鼠用载体、RU 486（20 mg/kg）和S-P（50 mg/kg）单独或与皮质酮（3 mg/kg）组合处理。RU 486诱导垂体、海马和前额叶皮质中的糖皮质激素受体核转位和海马中的糖皮质激素受体-DNA结合，而在所分析的任何区域中均未观察到S-P对糖皮质激素受体核转位或DNA结合的影响。这些发现揭示了RU 486和S-P对参与体内下丘脑-垂体-肾上腺轴活性调节的区域的不同作用，并且鉴于这类化合物在治疗与下丘脑-垂体-肾上腺轴过度活跃相关的疾病中的潜在用途，它们是重要的。
The effects of RU486 and S-P, a more selective glucocorticoid receptor antagonist from Schering-Plough, were investigated on glucocorticoid receptor nuclear translocation and DNA binding. In the in vitro study, AtT20 cells were treated with vehicle or with RU486, S-P or corticosterone (3–300 nM) or co-treated with vehicle or glucocorticoid receptor antagonists (3–300 nM) and 30 nM corticosterone. Both glucocorticoid receptor antagonists induced glucocorticoid receptor nuclear translocation but only RU486 induced DNA binding. RU486 potentiated the effect of corticosterone on glucocorticoid receptor nuclear translocation and DNA binding, S-P inhibited corticosterone-induced glucocorticoid receptor nuclear translocation, but not glucocorticoid receptor-DNA binding. In the in vivo study, adrenalectomized rats were treated with vehicle, RU486 (20 mg/kg) and S-P (50 mg/kg) alone or in combination with corticosterone (3 mg/kg). RU486 induced glucocorticoid receptor nuclear translocation in the pituitary, hippocampus and prefrontal cortex and glucocorticoid receptor-DNA binding in the hippocampus, whereas no effect of S-P on glucocorticoid receptor nuclear translocation or DNA binding was observed in any of the areas analysed. These findings reveal differential effects of RU486 and S-P on areas involved in regulation of hypothalamic–pituitary–adrenal axis activity in vivo and they are important in light of the potential use of this class of compounds in the treatment of disorders associated with hyperactivity of the hypothalamic–pituitary–adrenal axis.
类固醇拮抗剂 RU486 对糖皮质激素和孕激素受体发挥不同的作用。
影响因子：
4.8
作者：
Beck,CA;Estes,PA;Bona,BJ;Muro-Cacho,CA;Nordeen,SK;Edwards,DP
通讯作者：
Edwards,DP
用抗糖皮质激素 RU 38486 标记的人淋巴 (CEM-C7) 细胞质受体的体外激活和 DNA 结合亲和力。
DOI：
10.1016/0022-4731(86)90446-2
发表时间：
1986
期刊：
Journal of steroid biochemistry
影响因子：
--
作者：
Schmidt,TJ
通讯作者：
Schmidt,TJ