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

Laboratories of Medical Biochemistry, Immunology, and Biochemical Endocrinology, The Rockefeller University New York, New York 10021

Address all correspondence and requests for reprints to: Richard Bucala, Laboratory of Medical Biochemistry, Rockefeller University, Box 277, 1230 York Avenue, New York, New York 10021

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

^* This work was supported by the Kroc Foundation and Grant CA-22795.

Received August 30, 1984.

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