Estrogen modulates ileal basolateral membrane lipid dynamics and Na+-K+-ATPase activity

The effects of ethinyl estradiol, a synthetic estrogen with cholestatic properties and a propensity to alter hepatocyte and ileal brush-border membrane fluidity, on lipid structure and Na+-K+-ATPase activity of rabbit small intestinal basolateral membranes were determined. Utilizing the fluorophores 1,6-diphenyl-1,3,5-hexatriene and DL-12-(9-anthroyl)stearic acid, increases in fluorescence anisotropy, the reciprocal of fluidity, were found in basolateral membranes and in membrane lipid liposomes isolated from ileum. Fluidity alterations were accompanied by a marked decrease in bilayer phospholipids (0.37 vs. 0.48 mumol/mg protein; P less than 0.01) and an increase in both the cholesterol-to-phospholipid molar ratio (0.85 vs 0.61; P less than 0.02) and membrane saturated fatty acid content. Estrogen-mediated physicochemical changes were associated with a significant reduction in ileal basolateral membrane Na+-K+-ATPase specific activity (100.0 vs. 185.8 nmol Pi.min-1.mg protein-1; P less than 0.02). Control values both for fluorescence anisotropy and for Na+-K+-ATPase specific activity were restored after in vitro membrane fluidization with benzyl alcohol. The data therefore indicate that ethinyl estradiol effects on basolateral membrane lipid dynamics are confined to the ileum and are associated with inhibition of Na+-K+-ATPase activity. These structural and functional changes appear to be related, in part, to specific modifications in the availability of phospholipid after estrogen treatment.