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 17beta-estradiol (17beta-E2). Both floating and differentiating neurospheres expressed estrogen receptors (ERs) alpha and beta. The initial phases of differentiation coincided with a peak of ERalpha expression as by Western blot analysis. Treatment with 10 nM 17beta-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 17beta-E2 was characterized by a highly differentiated phenotype and intense immunostaining as by immunocytochemistry and flow cytometry. These cells co-expressed ERalpha and were positive to BrdU. 17beta-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 microtubule-associated protein 2 (MAP2) staining. Our results point to a key role for ERalpha during initial phases of differentiation of brain cells and to an effect of 17beta-E2 that sequentially involves both glia and neurons.
Merlo
Sara
S
Department of Experimental and Clinical Pharmacology, University of Catania, Viale Andrea Doria 6, 95125 Catania, Italy.
Calafiore
Marco
M
Vancheri
Carlo
C
Luigi Canonico
Pier
P
Copani
Agata
A
Sortino
Maria-Angela
MA
D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism*; D005434:Flow Cytometry; D000077267:Fulvestrant; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004965:Estrogen Antagonists; D004967:Estrogens; D005904:Glial Fibrillary Acidic Protein; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D004958:Estradiol