Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Estradiol metabolism in 10 patients with systemic lupus erythematosus (SLE) and 29 normal controls was studied by measurement of urinary metabolites after injection of labeled 3H-estradiol. Patients with SLE manifested increased 16-hydroxylation of estrone. Diseases men differed from diseases women to the extent that only 16 alpha-hydroxyestrone was elevated in men, whereas women had elevations of both 16 alpha-hydroxyestrone and estriol. These data suggest that patients with SLE have abnormal patterns of estradiol metabolism, leading to increased estrogenic activity.
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PMID:Alterations of estrogen metabolism in systemic lupus erythematosus. 50 72

Recent studies have demonstrated that many patients with SLE have elevated plasma levels of the minor oestrogen metabolite 16 alpha-hydroxyestrone (16 alpha OHE). This oestrogen is unique in its ability to react with lysine residues and form stable, covalent Heyns products with proteins. Increased levels of 16 alpha OHE-modified proteins have been found to occur on the membranes of red cells and lymphocytes in patients with SLE. In the present study, patient and control sera were analysed for the presence of circulating immunoglobulins which react with an oestrogen hapten. Anti-oestrogen antibodies were detected in 26% (9/34) of male and female SLE patients, and were found to correlate both with levels of plasma 16 alpha OHE (P less than 0.001) and with the presence of active disease (P less than 0.005). Surprisingly, this antibody activity was also observed in 25% (13/52) of normal, disease-free women who had a history of oral contraceptive use. No detectable activity was observed in normal men, women who had not taken oral contraceptives, or patients with a variety of other immunological diseases. The possible role of anti-oestrogen antibodies in both the hormonal exacerbation of SLE and in the long-term sequelae of oral contraceptive usage is discussed.
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PMID:Anti-oestrogen antibodies in users of oral contraceptives and in patients with systemic lupus erythematosus. 362 71

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.
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PMID:Increased levels of 16 alpha-hydroxyestrone-modified proteins in pregnancy and in systemic lupus erythematosus. 392 Feb 33

A radioimmunoassay for the feminizing metabolite 16 alpha-hydroxyestrone was applied to a variety of sera from healthy volunteers, patients with active or inactive systemic lupus erythematosus (SLE), and patients with other rheumatic diseases. A significant increase in this metabolite was detected in patients with SLE, especially those with active disease, compared with normal controls (P less than 0.001). SLE patients were categorized as having either active or inactive disease by clinical and laboratory criteria. Many patients who had clinically and serologically active disease were found to have normal levels of this estrogenic metabolite, and several explanations for these differences are explored in this report. Despite a poor correlation of hormone levels with age, antibody levels, or complement levels in patients with SLE, those patients with the highest levels of hormone were among those whose disease was clinically most active.
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PMID:Determination of 16 alpha-hydroxyestrone by radioimmunoassay in systemic lupus erythematosus. 405 23

Disturbed estrogen metabolism leading to increased 16 alpha-hydroxyestrone (16 alpha-OHE) has been described in patients with systemic lupus erythematosus and mammary carcinoma. Previous studies showed the formation of covalent complexes between 16 alpha-OHE and nonspecific cellular membrane proteins. The present study is concerned with the interaction of 16 alpha-OHE and histones. Covalent adduct formation between 16 alpha-OHE and individual histones was maximal with H1 histone. Other endogenous estrogens such as estrone, estradiol, and estriol did not interact with histones and form covalent adducts, nor did they interfere with the interaction of 16 alpha-OHE with these nuclear proteins. The evidence supports that the adduct formation between 16 alpha-OHE and histones proceeds via a stabilized Schiff base and subsequent rearrangement. This adduct formation which may have in vivo analogues may represent a mechanism for cellular transformation by this estrogen metabolite.
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PMID:Interaction of histones with estrogens. Covalent adduct formation with 16 alpha-hydroxyestrone. 409 52

Metabolism of estradiol in men with cirrhosis and subjects with systemic lupus erythematosus results in an excessive formation of 16 alpha-hydroxyestrone. Examination of the biological activity of this metabolite showed that it is a potent uterotropic agent and that it exhibits minimal affinity for the human sex hormone-binding globulin. These biological characteristics are consistent with a hyperestrongenic response to the substance, which may be reflected in the pathology and etiology of these diseases.
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PMID:Biological properties of 16 alpha-hydroxyestrone: implications in estrogen physiology and pathophysiology. 719 Sep 77