Estrogen mitigates leptin's effect on blood pressure through the SOCS3 signaling cascade

Estrogen has been purported to play a protective role against high blood pressure ‐ a possible explanation for the reduced prevalence of hypertension among pre‐menopausal women as compared to aged‐matched men. The loss of endogenous estrogen during menopause is correlated with a striking increase in the incidence of hypertension in women ‐ a leading risk factor of heart failure, stroke, and kidney disease. Thus, it is imperative to identify how estrogen attenuates hypertension. Our studies have demonstrated that leptin plays a significant role in augmenting blood pressure in the absence of estrogen. Bilateral ovariectomized (OVX) female rats were used to investigate the hypothesis that estrogen can mitigate leptin‐induced hypertension by increasing the expression of Suppressor of Cytokine Signaling 3 (SOCS3). SOCS3 is an inhibitor of the JAK/STAT signaling, a key pathway through which leptin increases blood pressure. OVX and control animals either received a sole intracerebroventricular injections of saline, leptin or estrogen, or a combination of saline/leptin or estrogen/leptin. Thirty minutes later, the hypothalami of animals that received a single injection were extracted and prepared for western blot analysis. Brains of the animals from the dual‐injection group were perfused and extracted for immunohistochemistry. Western blot analysis demonstrated that estrogen increases the expression of hypothalamic SOCS3 in the OVX group. Histological staining demonstrated that pretreatment with estrogen attenuated neuronal activation by leptin. Taken together, these data suggest that estrogen can attenuate leptin's effect on blood pressure by increasing the expression of SOCS3. Support or Funding Information Supported by The Iowa Osteopathic Educational Research Foundation This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .