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

International Journal of Molecular Sciences

Makiko Okada¹  Akihisa Makino¹  Mitsunari Nakajima²  Satoshi Okuyama²  Shoei Furukawa¹ 

[1] Laboratory of Molecular Biology, Department of Biofunctional Analysis, Gifu Pharmaceutical University, Gifu, Japan; E-Mails:;Department of Pharmaceutical Pharmacology, Faculty of Pharmaceutical Sciences, Matsuyama University, Ehime, Japan; E-Mails:

关键词: 17β-estradiol;    bisphenol A;    estrogen;    neural stem cell;    oligodendrocytes;    proliferation;    differeciation;   

DOI  :  10.3390/ijms11104114

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2010 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.