title: Estrogen stimulates proliferation and differentiation of neural stem/progenitor cells through different signal transduction pathways.
abstract: Our previous study indicated that both 17β-estradiol (E2), known to be an endogenous estrogen, and bisphenol A (BPA), known to be a xenoestrogen, could positively influence the proliferation or differentiation of neural stem/progenitor cells (NS/PCs). The aim of the present study was to identify the signal transduction pathways for estrogenic activities promoting proliferation and differentiation of NS/PCs via well known nuclear estrogen receptors (ERs) or putative membrane-associated ERs. NS/PCs were cultured from the telencephalon of 15-day-old rat embryos. In order to confirm the involvement of nuclear ERs for estrogenic activities, their specific antagonist, ICI-182,780, was used. The presence of putative membrane-associated ER was functionally examined as to whether E2 can activate rapid intracellular signaling mechanism. In order to confirm the involvement of membrane-associated ERs for estrogenic activities, a cell-impermeable E2, bovine serum albumin-conjugated E2 (E2-BSA) was used. We showed that E2 could rapidly activate extracellular signal-regulated kinases 1/2 (ERK 1/2), which was not inhibited by ICI-182,780. ICI-182,780 abrogated the stimulatory effect of these estrogens (E2 and BPA) on the proliferation of NS/PCs, but not their effect on the differentiation of the NS/PCs into oligodendroglia. Furthermore, E2-BSA mimicked the activity of differentiation from NS/PCs into oligodendroglia, but not the activity of proliferation. Our study suggests that (1) the estrogen induced proliferation of NS/PCs is mediated via nuclear ERs; (2) the oligodendroglial generation from NS/PCs is likely to be stimulated via putative membrane-associated ERs.
authors.affiliation: Laboratory of Molecular Biology, Department of Biofunctional Analysis, Gifu Pharmaceutical University, Gifu, Japan; E-Mails: miyufreia@yahoo.co.jp (M.O.); makino-akihisa@jpo.go.jp (A.M.); furukawa@gifu-pu.ac.jp (S.F.).
authors.forename: Makiko
authors.initials: M
authors.lastname: Okada
authors.forename: Akihisa
authors.initials: A
authors.lastname: Makino
authors.forename: Mitsunari
authors.initials: M
authors.lastname: Nakajima
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okuyama
authors.forename: Shoei
authors.initials: S
authors.lastname: Furukawa
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Furukawa
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D000077267:Fulvestrant; D020935:MAP Kinase Signaling System; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D055495:Neurogenesis; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D013687:Telencephalon / Q000166:cytology / Q000196:embryology / Q000378:metabolism
chemical_list: D004967:Estrogens; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D004958:Estradiol