Estrogen Signaling
Estrogen receptor-mediated regulation of reproduction, bone, and cardiovascular health.
Overview
Estrogens (primarily 17β-estradiol/E2) are synthesized from androgens by aromatase (CYP19A1). Classical signaling involves E2 binding nuclear receptors ERα and ERβ, which dimerize and bind estrogen response elements (EREs) to regulate transcription. Rapid non-genomic signaling occurs through membrane-associated ER and GPER (GPR30), activating MAPK, PI3K, and cAMP pathways. ERα and ERβ have distinct tissue distributions and sometimes opposing effects.
Cellular Location
Nucleus (genomic), membrane (non-genomic)
Clinical Significance
ERα drives ~75% of breast cancers; tamoxifen (SERM) and aromatase inhibitors are mainstay breast cancer therapies; estrogen protects against osteoporosis and cardiovascular disease premenopausally; HRT debates.