Increased Levels of 16α-Hydroxyestrone-Modified Proteins in Pregnancy and in Systemic Lupus Erythematosus*

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Abstract
The ketolic estrogen 16α-hydroxyestrone (16αOHE) reacts with lysine residues, forming stable covalent adducts with proteins. To determine the extent of protein modification by 16αOHE in vivo, we measured the level of 16αOHElysine 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 16αOHE. 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 16αOHE led to increased formation of 16αOHE-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 16αOHE-lysine than normal women (normal, 5.2 pmol 16αOHE-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 16αOUE, these measurements provide a useful indicator of the long term 16aOHE status of an individual. The modification of proteins by 16αOHE may be a link in the relationship between female hormones, pregnancy, and systemic lupus erythematosus.