Endocrine Abstracts

We have previously demonstrated that in experimental Parkinson’s disease local production of oestrogens protects against striatal dopamine loss in vivo (Gillies GE. et al. Pharmacol Biochem Behav. 2004;78:513–22). As neurodegenerative disease is invariably accompanied by neuroinflammation, much interest has focused on oestrogen receptor (ER)-dependent suppression of inflammatory activation of microglia, the primary innate immune cell-type in the brain, which, when activated, can release neurotoxic inflammatory molecules that exacerbate neurodegeneration (L’Episcopo F et al. CNS & Neurological Disorders - Drug Targets;2010:349–372). Far less attention has been given to the protective role of microglia which, we have shown, includes the phagocytic removal of apoptotic neurones before they can trigger damaging inflammatory responses (McArthur et al. J.Immunol. 2010;185:6317–28). Therefore, the present study investigated the hypothesis that oestrogenic compounds would modify the ability of microglia (BV2 cell line to phagocytose dopamine-producing neurone-like cells (PC12 cells) in which apoptosis was induced by the dopaminergic-selective neurotoxin, 6-hydroxydopamine (McArthur et al. J.Immunol. 2010;185:6317–28). 17β-oestradiol and the ERβ-selective agonist, DPN, dose-dependently enhanced phagocytosis, and the ERβ-selective antagonist (PHTPP) reversed this effect. The ERα-selective agonist, PPT, had no effect, whereas G1, a selective agonist at the putative membrane ER, GPR30, suppressed phagocytosis. Furthermore, a selective GPR30 antagonist (G15) augmented the ability of oestradiol to promote phagocytosis. Together, for the first time, these data a) demonstrate a potent effect of ERβ-signalling to promote microglial phagocytosis of injured neuronal cells, b) reveal that oestradiol may also suppress phagocytosis via GPR30 signalling and c) suggest novel mechanisms which may contribute to the neuroprotective effects of oestrogens, with potential for therapeutic exploitation in a much needed area. Acknowledgements: SV was in receipt of SfE Summer Studentship.

Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.