Fig. 5.

Schematic overview of estrogen/Tamoxifen interaction in a fibrogenic context. 1. Direct nuclear translocation and binding of estrogen/ERα complex to the Estrogen Responsive Element (ERE). 2. Estrogen/ERα complex binding to the Renin Enhancer Hormone Response Element (REHRE). 3. Estrogen/ERα complex modulated SMAD2/3 and ERK1/2 binding to SMAD Binding Element (SBE). 4. ERα independent binding of estrogen to G-protein coupled receptor 30., 5. Estrogen/GPR30 or estrogen/ERα complex mediated modulation of Src/EGFR interaction leading to downstream alterations in Serum Response Element (SRE) binding op MAPK. * Complex binding with ERE, REHRE, SBE or SRE respectively leads to modulation of processes involved in fibrosis (e.g. proliferation, differentiation, transcription including ECM production or infiltration/migration). Red lines indicate tamoxifen inhibition. Dashed red line indicates Tamoxifen mediated epigenetic alterations resulting in prolonged tamoxifen effects