In patients with
systemic lupus erythematosus, the female-to-male ratio 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 high susceptibility of female mice to the development of
glomerulonephritis after induction of
chronic graft-versus-host disease (GVHD), compared with male mice. In order to unravel further this gender-related difference (C57B1/10*DBA/2)F1 hybrid mice were either castrated or ovariectomized and treated with 17beta-ethinyloestradiol or
testosterone-decanoate preceding the induction of chronic GVHD.
Testosterone-decanoate reduced significantly the development of
albuminuria in females. In contrast,
proteinuria of 17beta-ethinyloestradiol-treated female mice was in the same range as that of
sham-operated mice.
Autoantibody levels against glomerular basement membrane, renal tubular epithelium, dsDNA and ssDNA, as determined by ELISA, were higher in 17beta-ethinyloestradiol-treated female mice than in all other groups. Immunofluorescence studies showed the presence of
immunoglobulin and
complement deposits in glomeruli of all animals, without significant differences between the experimental groups. Our findings confirm earlier observations, in that
testosterone-decanoate is shown to be an inhibitory compound, whereas 17beta-ethinyloestradiol has stimulating properties in autoimmunity. Moreover, our results show for the first time differential hormonal effects on
autoantibody levels and
proteinuria in experimental
lupus nephritis.