Fig. 1.

Schematic representation of the molecular mechanisms of estrogen receptors. The classical pathway of estrogen signaling is ligand-dependent activation of estrogen receptors (ERs) and direct genomic effects on gene regulation by binding estrogen response elements (ERE). The ligand-dependent indirect genomic regulation of gene transcription includes interaction with other transcription factors (TF). In ligand-dependent signaling the ligand activates either membrane-associated classical ERs and/or the G-protein-coupled receptor, GPR30, to initiate signaling cascades via second messengers. This leads to rapid physiological response without involving gene regulation. The ligand-independent pathway can be stimulated by other signaling pathways, such as growth factor signaling, and elicis both genomic and non-genomic effects. The activated kinases phosphorylate estrogen receptors, initiating dimerization and regulation of gene transcription or activation of second messengers. (Adapted from Heldring et al., 2007).