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Patients with Rheumatoid Arthritis and Systemic Lupus Erythematosus Have Increased Renal Excretion of Mitogenic Estrogens in Relation to Endogenous Antiestrogens
CLAUDIA WEIDLER, PETER HÄRLE, JOERG SCHEDEL, MARTIN SCHMIDT, JÜRGEN SCHÖLMERICH, and RAINER H. STRAUB
ABSTRACT. Objective. In patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), 17ß-estradiol was thought to play a dual pro- and antiinflammatory role depending on its concentration or probably conversion to downstream mitogenic 16a-hydroxyestrone or naturally occurring antiestrogens such as 2-hydroxyestrone. We compared renal excretion of these 2 types of estrogens in healthy subjects and patients with RA and SLE. Methods. In a prospective study with 30 patients with RA, 32 with SLE, and 54 healthy subjects, we measured urinary levels of 16a-hydroxyestrone and 2-hydroxyestrogens by enzyme immunoassay. We studied renal excretion to estimate the time-integral of hormone production. Results. Urinary concentration and total urinary loss of 2-hydroxyestrogens was 10 times higher in healthy subjects compared to patients with either SLE or RA irrespective of prior prednisolone treatment or sex. The urinary concentration and loss of 16a-hydroxyestrone did not differ between healthy subjects and patients with RA/SLE. The ratio of urinary 16a-hydroxyestrone/2-hydroxyestrogens was more than 20 times higher in RA and SLE than healthy subjects irrespective of prior glucocorticoid treatment or sex. Conclusion. This study in RA and SLE patients clearly demonstrates a large shift to mitogenic estrogens in relation to endogenous antiestrogens. Both steroids are converted from the precursor 17ß-estradiol and estrone. In patients with RA and SLE, the magnitude of conversion to the mitogenic 16a-hydroxyestrone is greatly upregulated, which likely contributes to maintenance of the proliferative state in these diseases. (J Rheumatol 2004;31:489-94) Key Indexing Terms:
RHEUMATOID ARTHRITIS
From the Department of Internal Medicine I, Laboratory of Neuroendocrinoimmunology, University Medical Center Regensburg; and the Department of Biochemistry II, University Hospital of Friedrich-Schiller University, Jena, Germany. R.H. Straub and M. Schmidt are supported by a grant from the Deutsche Forschungsgemeinschaft (DFG Str 511/10-1 and DFG Schm 1611/1-1). C. Weidler, Graduate PhD Student; J. Schedel, Fellow of Rheumatology; P. Härle, Fellow of Rheumatology; J. Schölmerich, MD, Professor, Head of Department; R.H. Straub, MD, Professor of Experimental Medicine, Rheumatologist, Department of Internal Medicine I, University Medical Center Regensburg; M. Schmidt, PhD, Biochemistry II, University Hospital, Friedrich-Schiller-University Jena. Address reprint requests to Dr. R.H. Straub, Department of Internal Medicine I, University Medical Center, D-93042 Regensburg, Germany. E-mail: rainer.straub@klinik.uni-regensburg.de Submitted March 21, 2003; revision accepted August 28, 2003. |