Astrocyte-like cells as a main target for estrogen action during neuronal differentiation

Neurospheres from the subventricular zone of adult mice were used as an experimental model to analyse the early differential effects of 17 beta-estradiol (17 beta-E2). Both floating and differentiating neurospheres expressed estrogen receptors (ERs) alpha and beta. The initial phases of differentiation coincided with a peak of ER alpha expression as by Western blot analysis. Treatment with 10 nM 17 beta-E2 induced a significant increase in the glial fibrillary acidic protein (GFAP)-positive population and a greater expression of GFAP, an effect sensitive to the estrogen receptor antagonist ICI 182,780. The GFAP-positive cell population induced by 17 beta-E2 was characterized by a highly differentiated phenotype and intense inummostaining as by immunocytochemistry and flow cytometry. These cells co-expressed ER alpha and were positive to BrdU. 17 beta-E2 also affected neuronal differentiation by rapidly and transiently increasing the percentage of polysialylated-neural cell adhesion molecule (PSA-NCAM) -positive progenitors, and by accelerating the appearance of a mature neuronal phenotype, as evaluated by micrombule-associated protein 2 (MAP2) staining. Our results point to a key role for ER alpha during initial phases of differentiation of brain cells and to an effect of 17 beta-E2 that sequentially involves both glia and neurons