Oestradiol regulates β-catenin-mediated transcription in neurones.

Oestradiol acts in the brain by multiple mechanisms, including the regulation of transcriptional activity through classical oestrogen receptors, α and β, and by the activation of membrane/cytoplasm-initiated signalling cascades. In neuroblastoma cells, primary neurones in culture and in the brain in vivo, oestradiol activates the phosphoinositide 3-kinase/Akt/glycogen synthase kinase 3 signalling pathway by a mechanism involving oestrogen receptor α. Through this pathway, oestradiol regulates the stability of β-catenin, induces the translocation of β-catenin to the cell nucleus and regulates β-catenin-mediated transcription through the T cell factor/DNA complex. Genomic analyses in neuroblastoma cells have revealed that the set of genes regulated by oestradiol through β-catenin is not identical to that regulated by the Wnt signalling pathway, revealing a new mechanism for oestradiol signalling in neurones.