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.