Increased levels of 16 alpha-hydroxyestrone-modified proteins in pregnancy and in systemic lupus erythematosus

Abstract

The ketolic estrogen 16 alpha-hydroxyestrone (16 alpha OHE) reacts with lysine residues, forming stable covalent adducts with proteins. To determine the extent of protein modification by 16 alpha OHE in vivo, we measured the level of 16 alpha OHE-lysine present within proteins of varying half-lives obtained from normal subjects, patients with systemic lupus erythematosus (SLE), and pregnant women. The latter groups have higher than normal levels of plasma 16 alpha OHE. The proteins analyzed were membrane proteins of the red cell and the lymphocyte and basement membrane proteins of the glomerulus. We report that elevated levels of plasma 16 alpha OHE led to increased formation of 16 alpha OHE-protein adducts and that the level of these adducts increases with the half-life of the protein. In the case of erythrocyte membrane proteins, pregnant women and women with SLE had significantly higher mean levels of 16 alpha OHE-lysine than normal women (normal, 5.2 pmol 16 alpha OHE-lysine/mmol leucine; SLE, 15.7; pregnant, 24.9). A similar elevation in the modification of lymphocyte proteins in women was found (normal, 15.6; SLE, 40.5). Since the degree of protein modification also was dependent on the ambient level of free 16 alpha OHE, these measurements provide a useful indicator of the long term 16 alpha OHE status of an individual. The modification of proteins by 16 alpha OHE may be a link in the relationship between female hormones, pregnancy, and systemic lupus erythematosus.