Androgen Receptor and Estrogen Receptors

The androgen receptor is a nuclear hormone receptor that binds androgens (testosterone, dihydrotestosterone)[2][5]. Upon ligand binding, AR translocates to the nucleus, forms dimers, and binds specific DNA sequences (androgen response elements), thereby regulating transcription of androgen-responsive genes crucial in male differentiation, prostate development, and cancer progression[1][2][5]. Its functional domains include the N-terminal regulatory domain, DNA binding domain with zinc fingers, hinge region, and ligand binding domain—each contributing to receptor activation and regulation[1][2][5][6]. The estrogen receptor consists primarily of two isoforms: ERα and ERβ[3]. Both bind estrogens and, upon ligand engagement, dimerize and bind to DNA estrogen response elements, facilitating transcriptional activation or repression of genes implicated in reproduction, development, cell cycle regulation, and cancers[3]. They share structure with AR, including modular functional domains—ligand binding, DNA binding (with zinc fingers), and regulatory regions—which interact with coactivators or corepressors and undergo posttranslational modifications for fine-tuned control[3]. Both receptors are targeted pharmacologically in cancers and endocrine disorders, using agents that block ligand binding, impede nuclear localization, degrade the receptor, or modulate receptor signaling pathways[7].

Other names

NR3C4ESR1Estrogen receptor 1ESR2Estrogen receptor 2Nuclear hormone receptorsSteroid hormone receptors

Antagonism/inhibition of ligand binding (competitive inhibition); Prevention of nuclear translocation (especially used in AR antagonists); Downregulation/degradation of the receptor (SERDs for ER); Agonist/partial agonist activation (rarely therapeutic for AR/ER, but occurs in some drugs)