Effects of estrogen receptor subtype-selective agonists on autoimmune disease in lupus-prone NZB/NZW F1 mouse model
- PMID: 17336162
- DOI: 10.1016/j.clim.2007.01.008
Effects of estrogen receptor subtype-selective agonists on autoimmune disease in lupus-prone NZB/NZW F1 mouse model
Abstract
The specific roles of estrogen receptor (ER) subtypes alpha and beta in mediating estrogen's influences on lupus autoimmunity are unknown. Herein we found that ovariectomized NZB/NZW F1 mice treated with propyl pyrazole triol (ERalpha-selective agonist) had significantly shorter survival, earlier development of albuminuria, higher serum concentrations of total IgG and prolactin, increased serum levels of anti-DNA IgG3, IgG2a and IgG2b and decreased anti-DNA IgG1 level compared to vehicle controls. In contrast, diarylpropionitrile (ERbeta-selective agonist) administration significantly decreased serum anti-DNA IgG2b level but did not significantly affect serum levels of other anti-DNA IgG subclasses, serum total IgG or prolactin concentration, mortality or the occurrence of albuminuria. These findings suggest that ERalpha activation plays the predominant and immunostimulatory role in estrogen-mediated modulation of lupus while ERbeta activation appears to have a slightly immunosuppressive effect on this disease. ERalpha activation coincidentally increased serum prolactin concentrations and may accelerate lupus disease activity also through this mechanism.
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