DIFFERENTIAL-EFFECTS OF SEX-HORMONES ON AUTOANTIBODY PRODUCTION AND PROTEINURIA IN CHRONIC GRAFT-VERSUS-HOST DISEASE-INDUCED EXPERIMENTAL LUPUS NEPHRITIS

In patients with systemic lupus erythematosus, the female-to-male rati o is as high as 10:1. Sex hormones are thought to play a role in this difference in susceptibility. In a previous study, we demonstrated a h igh susceptibility of female mice to the development of glomerulonephr itis after induction of chronic graft-versus-host disease (GVHD), comp ared with male mice. In order to unravel further this gender-related d ifference (C57B1/10DBA/2)F-1 hybrid mice were either castrated or ova riectomized and treated with 17 beta-ethinyloestradiol or testosterone -decanoate preceding the induction of chronic GVHD. Testosterone-decan oate reduced significantly the development of albuminuria in females. In contrast, proteinuria of 17 beta-ethinyloestradiol-heated female mi ce was in the same range as that of sham-operated mice, Autoantibody l evels against glomerular basement membrane, renal tubular epithelium, dsDNA and ssDNA, as determined by ELISA, were higher in 17 beta-ethiny loestradiol-treated female mice than in all other groups. Immunofluore scence studies showed the presence of immunoglobulin and complement de posits in glomeruli of all animals, without significant differences be tween the experimental groups, Our findings confirm earlier observatio ns, in that testosterone-decanoate is shown to be an inhibitory compou nd, whereas 17 beta-ethinyloestradiol has stimulating properties in au toimmunity. Moreover, oar results show for the first time differential hormonal effects on autoantibody levels and proteinuria in experiment al lupus nephritis.