G-protein-coupled Estrogen Receptor (GPER/GPR30): The Estrogen Receptor That Doesn’t Act Like an Estrogen Receptor / Kim J, Szinte JS, Boulware MI, Frick KM. 17β-Estradiol and Agonism of G-protein-Coupled Estrogen Receptor Enhance Hippocampal Memory via Different Cell-Signaling Mechanisms. J Neurosci. 2016 Mar 16;36(11):3309-21. doi: 10.1523/JNEUROSCI.0257-15.2016.

Jaekyoon Kim published a new study in the journal of Neuroscience that aims to investigate the role of G-protein-coupled Estrogen Receptor (GPER/GPR30) in female mice hippocampal memory. The ability of 17β-estradiol (E2) to enhance hippocampal object recognition and spatial memory depends on rapid activation of extracellular signal-regulated kinase (ERK) in the dorsal hippocampus (DH). Although this activation can be mediated by the intracellular estrogen receptors ERα and ERβ, little is known about the role that the membrane estrogen receptor GPER plays in regulating E2-mediated memory formation. In this study, although GPER activation did enhance object recognition and spatial memory, it did so by activating different cell-signaling mechanisms from ERα, ERβ, or 17β-estradiol. The data indicate that GPER regulates memory independently from ERα and ERβ by activating c-Jun N-terminal kinase (JNK) signaling, rather than ERK signaling. Thus, the findings suggest that GPER in the DH may not function as an estrogen receptor to regulate object recognition and spatial memory.

Jaekyoon examined whether the putative membrane estrogen receptor GPER acts like the classical estrogen receptors, ERα and ERβ, to facilitate hippocampal memory in female mice. These data indicate that 17β-estradiol and GPER independently regulate hippocampal memory, and suggest that hippocampal GPER may not function as an estrogen receptor in the dorsal hippocampus. These findings are significant because they provide novel insights about the molecular mechanisms through which 17β-estradiol modulates hippocampal memory. Jaekyoon believes this can reveal a novel drug targets for reducing age-related memory decline in women.