Abstract：
The cellular response to the adrenal steroid aldosterone is mediated by the mineralocorticoid receptor (MR), a member of the nuclear receptor superfamily of ligand-dependent transcription factors. The MR binds more than one physiological ligand with binding at the MR determined by pre-receptor metabolism of glucocorticoid ligands by 11β hydroxysteroid dehydrogenase type 2. The MR has a wide tissue distribution with multiple roles beyond the classical role in electrolyte homeostasis including cardiovascular function, immune cell signaling, neuronal fate and adipocyte differentiation. The MR has three principal functional domains, an N-terminal ligand domain, a central DNA binding domain and a C-terminal, ligand binding domain, with structures having been determined for the latter two domains but not for the whole receptor. MR signal-transduction can be best viewed as a series of interactions which are determined by the conformation conferred on the receptor by ligand binding. This conformation then determines subsequent intra- and inter-molecular interactions. These interactions include chromatin, coregulators and other transcription factors, and additional less well characterized cytoplasmic non-genomic effects via crosstalk with other signaling pathways. This chapter will provide a review of MR structure and function, and an analysis of the critical interactions involved in MR-mediated signal transduction, which contribute to ligand- and tissue-specificity. Understanding the relevant mechanisms for selective MR signaling in terms of these interactions opens the possibility of novel therapeutic approaches for the treatment of MR-mediated diseases.
摘要：
肾上腺类固醇醛固酮的细胞反应是由盐皮质激素受体（MR）介导的，配体依赖性转录因子的核受体超家族成员。MR结合一种以上的生理配体，并在MR处通过11β羟基类固醇脱氢酶2型的糖皮质激素配体的受体前代谢确定结合。MR具有广泛的组织分布，除了在电解质稳态中的经典作用外，还具有多种作用，包括心血管功能。免疫细胞信号，神经元命运和脂肪细胞分化。MR有三个主要的功能域,N端配体结构域，一个中央DNA结合域和一个C末端，配体结合域，已经确定了后两个结构域的结构，但不是整个受体的结构。MR信号转导可以最好地视为一系列相互作用，这些相互作用由配体结合赋予受体的构象决定。这种构象然后决定随后的分子内和分子间相互作用。这些相互作用包括染色质，共调节因子和其他转录因子，以及通过与其他信号通路的串扰而表征较少的细胞质非基因组效应。本章将对MR结构和功能进行回顾，并分析了与MR介导的信号转导有关的关键相互作用，这有助于配体和组织特异性。根据这些相互作用了解选择性MR信号传导的相关机制为治疗MR介导的疾病开辟了新的治疗方法的可能性。
