Estrogen Receptor Beta and G‐Protein Coupled Estrogen Receptor are Located and Activated on Microglia by Estrogen

Abstract

Upon menopause, women have an increased risk of cardiovascular disease, in part due to the decrease in estrogen production that occurs. While estrogen's cardioprotective effects have been known for many years, the exact mechanism of this protection is still under investigation. Estrogen receptors have been detected in locales in the central nervous system that are critical in the regulation of arterial pressure and sympathetic nervous activity, particularly the rostral ventrolateral medulla (RVLM) and paraventricular nucleus (PVN) of the hypothalamus. Animal models of menopause implicate over activity of the sympathetic nervous system contributes to hypertension. Microglia are believed to be the resident immune cells of the brain. In previous studies, activated glia have been shown to contribute to increased neuronal tone and excitability in the PVN and RVLM and increased sympathetic activity, potentially through the release of pro‐inflammatory cytokines. The role of microglia in hypertension is not clear. The overall objective of these studies is to investigate if estrogen can regulate the activity of microglia. We sought to evaluate how estrogen regulates its cognate receptors using an immortalized microglia 10‐day old female mouse cell line (EOC2). Utilizing immunohistochemical and western blot techniques, our data demonstrate that the microglia cell line expressed estrogen receptor beta (ERβ) and G‐Protein coupled Estrogen Receptor (GPER). Exposing the cells to 10nM of estrogen for 15 minutes demonstrated that estrogen activates the microglia and initiates ERβ translocation from the membrane to the cytosol. We found a dose (1, 10 and 100 nM) and time (5, 15, 30 and 60 minute) dependent change in the protein level of GPER and ERβ. These results demonstrate that estrogen exposure can activate microglial cells and increase expression of estrogen receptors. Future studies will examine if the activation of microglia by estrogen alters the release of cytokines and thus may modulate neuronal function. These findings will contribute to the pivotal role estrogen plays in central blood pressure regulation and will undoubtedly shed light on possible mechanisms of menopause‐induced hypertension.Support or Funding InformationS Clayton DMU IOERM Barnes DMU IOERThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.