Glucocorticoid receptor (GR) (GR)

The Glucocorticoid receptor (GR), encoded by the NR3C1 gene, is a member of the nuclear receptor superfamily that functions as a ligand-dependent transcription factor (UniProt P04150). Upon binding to endogenous glucocorticoids like cortisol or synthetic agonists, the receptor undergoes a conformational change, dissociates from heat shock proteins, and translocates from the cytoplasm to the nucleus (PubMed: 29126018). In the nucleus, it regulates the expression of thousands of genes involved in metabolism, development, and immune function by binding to specific DNA sequences or interacting with other transcription factors (StatPearls: Physiology, Cortisol). GR is a primary therapeutic target for treating a wide range of inflammatory, allergic, and autoimmune conditions, as well as certain hematological malignancies like leukemia (PubMed: 30115704). However, the clinical utility of GR-targeted therapies is often limited by significant side effects, including metabolic dysfunction, bone loss, and hypothalamic-pituitary-adrenal (HPA) axis suppression (PubMed: 28414319). Current research focuses on developing selective glucocorticoid receptor modulators (SEGRMs) that aim to dissociate the beneficial anti-inflammatory effects from the adverse metabolic outcomes (PubMed: 30115704).

Other names

Nuclear receptor subfamily 3 group C member 1NR3C1Glucocorticoid receptor alphaGRLGCCR

Ligand-activated transcription factor that modulates gene expression via transactivation (binding to glucocorticoid response elements) and transrepression (antagonizing other transcription factors like NF-kappaB and AP-1) (PubMed: 29126018).