Glucocorticoids are among the most prescribed drugs worldwide for the treatment of numerous immune and inflammatory disorders. They exert their actions by binding to the glucocorticoid receptor (GR), a member of the nuclear receptor superfamily. There are several GR isoforms resulting from alternative RNA splicing and translation initiation of the GR transcript. Additionally, these isoforms are all subject to several transcriptional, post-transcriptional, and post-translational modifications, all of which affect the protein's stability and/or function. In this review, we summarize recent knowledge on the distinct GR isoforms and the processes that generate them. We also review the importance of all known transcriptional, post-transcriptional, and post-translational modifications, including the regulation of GR by microRNAs. Moreover, we discuss the crucial role of the putative GR-bound DNA sequence as an allosteric ligand influencing GR structure and activity. Finally, we describe how the differential composition and distinct regulation at multiple levels of different GR species could account for the wide and diverse effects of glucocorticoids.

中文翻译：

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糖皮质激素受体的结构和调节的全面概述。

糖皮质激素是世界上用于治疗多种免疫和炎性疾病的处方最广泛的药物之一。它们通过与糖皮质激素受体（GR）结合而发挥作用，糖皮质激素受体是核受体超家族的成员。GR转录物的替代RNA剪接和翻译起始产生了几种GR亚型。另外，这些同工型都经受几种转录，转录后和翻译后修饰，所有这些均影响蛋白质的稳定性和/或功能。在这篇综述中，我们总结了关于不同GR异构体及其生成过程的最新知识。我们还审查了所有已知的转录，转录后和翻译后修饰的重要性，包括microRNA对GR的调控。此外，我们讨论了假定的GR绑定的DNA序列作为影响GR结构和活性的变构配体的关键作用。最后，我们描述了不同GR物种在多个水平上的差异组成和不同的调控如何解释糖皮质激素的广泛而多样的作用。