Fig. 1.

Sex differences in the signal transduction pathways of endothelial nitric oxide (NO) synthase (eNOS) activation in endothelial cells by estradiol and testosterone and the subsequent vascular response. Estradiol is generally thought to increase NO availability through genomic and nongenonimc pathways in both men and women, resulting in vasodilation. Testosterone has similar effects in men. Testosterone works through a separate pathway in women, resulting in reduced NO availability and impaired vasodilation. The dashed line indicates effects that are uncertain. ER, estrogen receptor; AR, androgen receptor; PI3K, phosphatidylinositol 3-kinase; GPER, G protein-coupled estrogen receptor 1.