Examining the effect of estradiol and sex on gene expression in the subfornical organ

Sex significantly influences rates of hypertension (high blood pressure), a major risk factor for cardiovascular disease that accounts for 1 out of every 3 deaths. In young adults, men are at a greater risk for hypertension. This sex difference, however, reverses around the time women reach menopause. This change highlights a critical role for estradiol in maintaining healthy blood pressure; as estradiol, levels drop during aging, blood pressure increases. Unfortunately, how gonadal hormones and biological sex control blood pressure is unclear. While multiple peripheral organs play important roles, the brain is the master regulator of fluid homeostasis. In particular, the Subfornical Organ (SFO), a small circumventricular nucleus in the forebrain, is critically involved in controlling the physiology and behavior involved in defending fluid balance. This pilot project will test the overarching hypothesis transcriptomic differences in genes known to be critical to fluid homeostasis are differentially expressed in the Subfornical Organ of male and female rats. To do this, our Primary Aim will examine transcriptomic differences in the SFO across sex and estradiol treatment and determine circuit level expression of these differentially expressed genes (DEGs) These experiments will establish key preliminary data that will be used to develop mechanistic hypotheses and drive subsequent extramural grant applications focused on understanding how estradiol and biological sex control fluid homeostasis.