1. Figure 2 Oestrogen receptor signalling pathways
Figure 2 | Oestrogen receptor signalling pathways. Oestrogen receptor (ER) signalling occurs through genomic and non-genomic mechanisms. In the genomic (classic) signalling pathway, ERs are activated by different ligands, of which oestradiol is the strongest natural ligand. Oestradiol binds to ERs located in the cytoplasm; the activated ERs dimerize and translocate into the nucleus where they activate or repress target genes within hours of ligand binding. Activated ERs can interact directly with oestrogen-responsive elements (EREs) or with other DNA-bound transcription factors. However, oestradiol can also exert transcriptional effects in an ER-independent manner. ER-mediated genomic actions can also occur independently from oestradiol. Growth factors can activate their specific receptors to initiate protein kinase cascades that phosphorylate (in the figure, indicated by the 'P') and activate ERs, which translocate into the nucleus to interact with EREs and mediate gene transcription. In non-genomic signalling pathways, ERs located at the cell membrane, generally in caveolae, initiate cytosolic signalling events that modulate protein phosphorylation and the activation of different protein kinases, thereby regulating second-messenger systems such as Ca2+, K+ and nitric oxide (NO), leading to the activation of tyrosine kinase receptors, epidermal growth factor receptor (EGFR), insulin-like growth factor 1 receptor (IGF1R) and protein kinase B (PKB). Oestrogenic signalling also occurs via membrane-bound G protein-coupled oestrogen receptor 1 (GPER1), which is localized at the cell membrane and on the endoplasmic reticulum. Oestradiol binds to GPER1 and activates multiple cellular effectors, such as JUN amino-terminal kinases (JNKs), mitogen-activated protein kinases (MAPKs), phosphoinositide 3-kinase (PI3K) and other rapid cellular processes. CAV1, caveolin 1.
Morselli, E. et al. (2017) The effects of oestrogens and their receptors on cardiometabolic health
Nat. Rev. Endocrinol. doi: /nrendo