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Int. J. Mol. Sci. 2010, 11(10), 4114-4123; doi:10.3390/ijms11104114
Article

Estrogen Stimulates Proliferation and Differentiation of Neural Stem/Progenitor Cells through Different Signal Transduction Pathways

1
,
1
,
2
,
2
,
1
 and
1,2,*
1 Laboratory of Molecular Biology, Department of Biofunctional Analysis, Gifu Pharmaceutical University, Gifu, Japan 2 Department of Pharmaceutical Pharmacology, Faculty of Pharmaceutical Sciences, Matsuyama University, Ehime, Japan
* Author to whom correspondence should be addressed.
Received: 13 October 2010 / Revised: 17 October 2010 / Accepted: 18 October 2010 / Published: 22 October 2010
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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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.
Keywords: 17β-estradiol; bisphenol A; estrogen; neural stem cell; oligodendrocytes; proliferation; differeciation 17β-estradiol; bisphenol A; estrogen; neural stem cell; oligodendrocytes; proliferation; differeciation
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Okada, M.; Makino, A.; Nakajima, M.; Okuyama, S.; Furukawa, S.; Furukawa, Y. Estrogen Stimulates Proliferation and Differentiation of Neural Stem/Progenitor Cells through Different Signal Transduction Pathways. Int. J. Mol. Sci. 2010, 11, 4114-4123.

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