Lupus: Why women?

Estrogens are believed to play a role in the etiology of both human and mur ine systemic lupus erythematosus (lupus, SLE), presumably through the agenc y of their cellular receptor proteins. There is now considerable interest i n the molecular mechanism of action of estrogens in immune tissues, particu larly with regard to autoimmune disorders, which are generally more prevale nt in women. In this laboratory, an attempt is being made to characterize e strogen receptors in murine models of SLE, namely NZB/W and MRL/MP-lpr/lpr mice, and to try to relate this to estrogen receptor function in vivo. It i s hypothesized that estradiol (EP), through its receptors, mediates the pro gression of murine SLE and that in autoimmune disease, the estrogen recepto r is functionally or structurally changed, or both. Initial studies suggest there are differences in estrogen receptors between BALB/c mice, which do not get autoimmune disease, and two strains that do, MRL/MP-lpr/lpr and NZB /W mice. There is evidence that in at least one model of SLE, the normal re gulation of estrogen action by progesterone may be impaired. In several lab oratories, attempts are being made to relate estrogen action to immune func tion and to autoimmune diseases. The study of estrogen action on the immune system may lead to the development of treatments that attenuate the immuno stimulant effects of Ep in autoimmune diseases such as SLE.