G protein-coupled estrogen receptor 1 negatively regulates the proliferation of mouse-derived neural stem/progenitor cells via extracellular signal-regulated kinase pathway

Abstract G protein-coupled estrogen receptor 1 (GPER1, also known as GPR30) has been reported to play a wide range of function in the central nervous system (CNS). However, whether GPER1 is expressed by neural stem/progenitor cells (NSPCs) and its role has not been established. Here, we found the expression of GPER1 in mouse-derived NSPCs via western blot and immunofluorescent staining. Moreover, we revealed that specific activation of GPER1 by the agonist G1 decreased the proliferation of NSPCs in a dose-dependent manner. The neurosphere formation assay and Ki67 staining further demonstrated that activation of GPER1 inhibited the proliferation of NSPCs. Additionally, the inhibitory effect of G1 on the proliferation of NSPCs could be blocked by the specific GPER1 antagonist G15. Intriguingly, ERK pathway was involved in the negative effect of GPER1 on the proliferation of NSPCs, because the phosphorylation level of ERK in NSPCs was remarkably decreased during G1 treatment. However, the antagonist G15 reversed the down-regulated level of p-ERK. Knock-down GPER1 also reversed the inhibitory effect of G1 on NSPCs proliferation. Together, our results provide the first evidence that GPER1 is expressed by NSPCs and its activation negatively modulates the proliferation of NSPCs, highlighting the importance of GPER1 in regulating NSPC behaviors.