Trapp T, Rupprecht R, Castrén M, Reul J M, Holsboer F
Max-Planck-Institute of Psychiatry, Department of Neuroendocrinology Munich, Germany.
Neuron. 1994 Dec;13(6):1457-62. doi: 10.1016/0896-6273(94)90431-6.
In the mammalian central nervous system, responsiveness to glucocorticoids is mediated by both the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). These pharmacologically distinct receptors are believed to bind to common response elements as homodimers. We provide evidence that MR and GR can form a heterodimeric complex with DNA-binding and transactivation properties different from those of the respective homodimers. There was a high degree of cooperativity of MR and GR in binding to a glucocorticoid response element. Transient transfection of a neuroblastoma cell line revealed a transcriptional response pattern of coexpressed MR and GR distinct from that obtained by MR or GR alone. Our findings demonstrate that heterodimerization of MR and GR is a hitherto unrecognized principle for the transcriptional regulation of glucocorticoid-responsive genes in tissue coexpressing these receptors.
在哺乳动物中枢神经系统中，对糖皮质激素的反应是由盐皮质激素受体（MR）和糖皮质激素受体（GR）介导的。这些药理学上不同的受体被认为以同二聚体形式结合到共同的反应元件上。我们提供的证据表明，MR和GR可以形成一种异二聚体复合物，其DNA结合和反式激活特性不同于各自的同二聚体。MR和GR在结合糖皮质激素反应元件时具有高度协同性。对神经母细胞瘤细胞系的瞬时转染显示，共表达的MR和GR的转录反应模式不同于单独的MR或GR所获得的模式。我们的研究结果表明，MR和GR的异二聚化是在共表达这些受体的组织中糖皮质激素反应性基因转录调控的一个迄今未被认识的机制。
