Departamento de Química Biológica, Universidad de Buenos Aires, Buenos Aires C1428EGA, Argentina.
Mol Cell Endocrinol. 2012 Feb 26;349(2):214-21. doi: 10.1016/j.mce.2011.10.026. Epub 2011 Nov 4.
The antagonism exerted by melatonin on the glucocorticoid response has been well established, being strongly dependent on the cellular context. Previously, we found that melatonin inhibits glucocorticoid receptor (GR) dissociation from the chaperone hetero-complex and nuclear translocation on mouse thymocytes. Here, by performing confocal fluorescence microscopy and the Number and Brightness assay we show that in newborn hamster kidney cells (BHK21) melatonin neither affects GR nuclear translocation nor GR homodimerization. Instead, co-immunoprecipitation studies suggest that physiological concentrations of melatonin impair GR interaction with the transcriptional intermediary factor 2 (TIF2). This melatonin effect was not blocked by the MT(1)/MT(2) receptor antagonist luzindole. Curiously, luzindole behaved as an antiglucocorticoid per se by impairing the glucocorticoid-dependent MMTV-driven gene expression affecting neither GR translocation nor GR-TIF2 interaction.
褪黑素对糖皮质激素反应的拮抗作用已经得到充分证实，并且强烈依赖于细胞环境。之前，我们发现褪黑素抑制糖皮质激素受体（GR）从伴侣异质复合物和核转位的解离在小鼠胸腺细胞上。在这里，通过共聚焦荧光显微镜和数量和亮度测定，我们表明在新生仓鼠肾细胞（BHK21）中，褪黑素既不影响 GR 核转位，也不影响 GR 同源二聚体化。相反，共免疫沉淀研究表明，生理浓度的褪黑素会损害 GR 与转录中介因子 2（TIF2）的相互作用。这种褪黑素的作用不会被 MT(1)/MT(2) 受体拮抗剂 luzindole 阻断。奇怪的是，luzindole 本身作为一种抗糖皮质激素，通过损害糖皮质激素依赖性 MMTV 驱动的基因表达而发挥作用，既不影响 GR 转位，也不影响 GR-TIF2 相互作用。
