Category: receptor_pharmacology
GR (NR3C1) is a ligand-activated nuclear transcription factor. Cortisol + synthetic glucocorticoids bind cytoplasmic GR → HSP90 release → nuclear translocation → GRE binding. Two modes: transactivation (positive regulation — metabolic + anti-inflammatory cytokine reduction) + transrepression (NF-κB + AP-1 tethering — anti-inflammatory). Therapeutic glucocorticoids: hydrocortisone (cortisol replacement), methylprednisolone (IV bolus for MS exacerbation, transplant rejection), prednisolone (active metabolite of prednisone — chronic immunosuppression), dexamethasone (long-acting, no mineralocorticoid activity, intracranial edema + COVID ARDS), inhaled (fluticasone, budesonide, beclomethasone, ciclesonide — high topical:systemic ratio for asthma/COPD), topical (clobetasol, betamethasone — DERM cluster). Fludrocortisone is mineralocorticoid-dominant.