Membrane impermeable BSA conjugated estrogen activated ERK1/2 and induced the transcription of a reporter gene driven by mouse c–fos promoter in human neuroblastoma cell line SK–N–SH (Watters et al. 1997). Estrogen induction of c–fos gene occurs through MAPK mediated Elk1 phosphorylation, which transactivates the serum response element (SRE) in proximal c–fos promoter (Duan et al. 2001). Previously, estrogen attenuated glutamate–induced neurons death, which is abolished by U0126, a potent MEK inhibitor (Yi et al. 2008). Moreover, estrogen protects glutamate–induced primary cortical neuron death by increasing activated ERK (pERK) (Singer et al. 1999).