Modulating glucocorticoid receptor actions in physiology and pathology: Insights from coregulators

Glucocorticoids (GCs) are a class of steroid hormones that regulate key physiological processes such as metabolism, immune function, and stress responses. The effects of GCs are mediated by the glucocorticoid receptor (GR), a ligand-dependent transcription factor that activates or represses the expression of hundreds to thousands of genes in a tissue- and physiological state-specific manner. The activity of GR is modulated by numerous coregulator proteins that interact with GR in response to different stimuli assembling into a multitude of DNA-protein complexes and facilitate the integration of these signals, helping GR to communicate with basal transcriptional machinery and chromatin. Here, we provide a brief overview of the physiological and molecular functions of GR, and discuss the roles of GR coregulators in the immune system, key metabolic tissues and the central nervous system. We also present an analysis of the GR interactome in different cells and tissues, which suggests tissue-specific utilization of GR coregulators, despite widespread functions shared by some of them.