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Estrogen Stimulates Proliferation and Differentiation of Neural Stem/Progenitor Cells through Different Signal Transduction Pathways
Laboratory of Molecular Biology, Department of Biofunctional Analysis, Gifu Pharmaceutical University, Gifu, Japan
Department of Pharmaceutical Pharmacology, Faculty of Pharmaceutical Sciences, Matsuyama University, Ehime, Japan
* Author to whom correspondence should be addressed.
Received: 13 October 2010; in revised form: 17 October 2010 / Accepted: 18 October 2010 / Published: 22 October 2010
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
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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.
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. International Journal of Molecular Sciences. 2010; 11(10):4114-4123.
Okada, Makiko; Makino, Akihisa; Nakajima, Mitsunari; Okuyama, Satoshi; Furukawa, Shoei; Furukawa, Yoshiko. 2010. "Estrogen Stimulates Proliferation and Differentiation of Neural Stem/Progenitor Cells through Different Signal Transduction Pathways." Int. J. Mol. Sci. 11, no. 10: 4114-4123.