Estrogen accelerates immune complex glomerulonephritis but ameliorates T cell-mediated vasculitis and sialadenitis in autoimmune MRL lpr/lpr mice.

Estrogen is known to influence immune responses in healthy subjects in a dichotomous fashion. Thus, in number of previous studies we and others have demonstrated that B cell activities are augmented after exposure to estrogen whereas T cell reactivity is suppressed. Furthermore, it has been shown that this hormone has significant impact on the course of certain human and experimental autoimmune diseases. In this study we report that treatment with physiological doses of estradiol exerts dichotomous effects on different manifestations of the lupus disease in MRL/l mice. On one hand immune complex-mediated glomerulonephritis was significantly accelerated. This outcome was due to polyclonal B cell activation with increased production of antibodies to double-stranded DNA and formation of circulating immune complexes. In contrast, T cell-mediated lesions such as focal sialadenitis, renal vasculitis, and periarticular inflammation were all significantly ameliorated in MRL/l mice exposed to estrogen. Thus, we were able to demonstrate that, within one subject and even within one organ, administration of estrogen leads to differential outcome of SLE morbidity. We propose that the differential effect of estrogen on the manifestations of the autoimmune disease of MRL/l mice is due to its dichotomous effects on B and T cell-mediated immune responses.     

A redox system for brain targeted estrogen delivery causes chronic body weight decrease in rats

The effects of 2 redox based carriers for brain directed delivery of estradiol (CDS-E2) and ethinyl estradiol (CDS-EE) on body weight were examined in rats. A single dose of CDS-E2 (3 mg/kg) decreased weight gain in castrate rats for at least 24 days. The dose response of weight gain and LH suppression were compared 12 days and 12 to 25 after CDS-E2 and CDS-EE, respectively, in ovariectomized (OVX) rats. Weight decrease was detected at a lower dose and was significant for longer after drug treatment than LH decrease. Both compounds were more potent than equimolar estradiol or estradiol valerate in reducing weight gain. Intact rats also showed decreased weight gain but were less sensitive to CDS-E2 compared to OVX rats. The effects appeared to be estrogen specific as carrier-linked testosterone had no effect on weight. The mechanisms of sustained and potent drug effects on weight are being explored.