Estrogen modulates phospholipid acylation in red blood cells: relationship to cell aging

Ethinyl estradiol administered in vivo to female rats resulted in a mild anemia with a 120% increase in reticulocytosis. Consistent with a previous study, the red blood cell cholesterol-to-phospholipid molar ratio was decreased by 25%, whereas fatty acyl incorporation was significantly increased into phosphatidylethanolamine (PE) and not into phosphatidylcholine (PC), the major acyl acceptor in red blood cells. Analysis of this estrogen-dependent acylation increase as a function of cell age indicated that it was not expressed in reticulocytes but in erythrocytes and was associated with cell aging. Estrogen was further shown to increase the red blood cell susceptibility to peroxidation generated by incubation with H2O2. Altogether, the results suggest that estrogen indirectly increases phospholipid acylation in red blood cells by decreasing protection against oxidative damage, thereby favoring the action of endogenous phospholipases against oxidized substrates. This occurs predominantly in PE of oldest cells because 1) PE, being more unsaturated than PC, is more sensitive to oxidation, and 2) susceptibility to oxidation increases with cell age.