Androgen receptor; Glucocorticoid receptor (AR; GR)

The Androgen receptor (AR; NR3C4) is a nuclear steroid hormone receptor that, upon binding androgens like testosterone and dihydrotestosterone, translocates to the nucleus, binds to androgen response elements, and regulates genes responsible for the development and maintenance of male characteristics as well as cell growth, particularly in prostate tissue[1][3][4][5]. The AR is modular with an N-terminal transactivation domain, a DNA-binding domain, and a ligand-binding domain, and regulates gene expression by recruiting coactivators or corepressors and initiating chromatin remodeling[1][3][5]. The Glucocorticoid receptor (GR; NR3C1) similarly acts as a ligand-dependent transcription factor, binding natural glucocorticoids such as cortisol. Upon activation, it translocates to the nucleus and regulates genes involved in glucose metabolism, immune response, cell survival, and stress responses. GR has tumor suppressive roles in normal tissues but may act as an oncogene in antiandrogen-resistant cancers[2][4][6]. GR is essential for mediating anti-inflammatory and immunosuppressive effects of steroid drugs[2][4]. Both receptors share a highly conserved DNA-binding domain and can recognize common hormone response elements, but chromatin context and coregulators drive their functional specificity[6][4]. They are clinically significant for therapy in prostate cancer, hormone disorders, inflammation, and immune modulation, but they also carry risks of resistance and systemic side effects[4][7][2].

Other names

NR3C4Androgen receptorNR3C1Glucocorticoid receptor

AR-targeting drugs: Inhibition of androgen binding; blockade of nuclear translocation; antagonist effects at ligand binding domain; promoting receptor degradation. GR-targeting drugs: Agonism or antagonism at the glucocorticoid binding site; modulation of gene transcription to suppress inflammation, immune responses, or cancer cell adaptation.