Role of estrogen receptor alpha in membrane-initiated signaling in neural cells: interaction with IGF-1 receptor.

The mechanisms of action of estradiol in the nervous system involve nuclear-initiated steroid signaling and membrane-initiated steroid signaling. Estrogen receptors (ERs) are involved in both mechanisms. ERalpha interacts with the signaling of IGF-1 receptor in neural cells: ERalpha transcriptional activity is regulated by IGF-1 receptor signaling and estradiol regulates IGF-1 receptor signaling. The interaction between ERalpha and the IGF-1 receptor in the brain may occur at the plasma membrane of neurons and glial cells. Caveolin-1 may provide the scaffolding for the interaction of different membrane-associated molecules, including voltage-dependent anion channel, ERalpha and IGF-I receptor.