Molecular pharmacology of glucocorticoids: recent advances and future perspectives

Abstract Glucocorticoids are one of the most widely used bullets for the treatment of inflammatory and immune disorders. They act by binding to their specific intracellular receptor, the glucocorticoid receptor (GR), which is a transcription factor belonging to the nuclear receptor superfamily. It is believed that the GR, upon binding ligand, elicits transcriptional regulation of target gene expression via orchestrated interaction with DNA, coregulators, other transcription factors, and chromatin. This model has raised the possibility that a certain class of ligand might variably modulate GR-mediated intracellular signals. Moreover, crystallographic analysis of the ligand-binding domain of the nuclear receptor has given structural insight into the ligand-dependent modularity of the receptor function. This advanced technology would allow the molecular pharmacologic development of a ligand that could dissociate therapeutic actions from the undesirable metabolic effects of glucocorticoids in the near future.