Estrogen induces rapid translocation of estrogen receptor β, but not estrogen receptor α, to the neuronal plasma membrane

Abstract

Estrogen receptors can activate transcription in the nucleus, and activate rapid signal transduction cascades in the cytosol. Multiple reports identify estrogen receptors at the plasma membrane, while others document the dynamic responses of estrogen receptor to ligand binding. However, the function and identity of membrane estrogen receptors remain controversial. We have used confocal microscopy and cell fractionation on the murine hippocampus-derived HT22 cell line and rat primary cortical neurons transfected with estrogen receptor–green fluorescent protein constructs to address the membrane localization of these receptors. We observe translocation of estrogen receptor beta (β) to the plasma membrane 5 min after exposure to 17β-estradiol, whereas estrogen receptor alpha (α) localization remains unchanged. Membrane localization of estrogen receptor β is transient, selective for 17β-estradiol, and is not blocked by ICI182,780. Inhibition of the mitogen-activated protein kinase pathway does not block estrogen-mediated estrogen receptor β membrane translocation, and in fact prolongs membrane localization. These data suggest that while both estrogen receptor α and estrogen receptor β can be present at the neuronal membrane, their presence is differentially regulated.