In 1896, physician George Beatson observed that removal of the ovaries caused regression of mammary tumors in women. His experiments were the first to establish a link between ovarian secretions and breast cancer. Later in the early 1930s, the “female” sex hormones, estrone and estriol, could be isolated from human pregnancy urine, followed by isolation of a third estrogen, estradiol (E2), from pig follicular fluid. Shortly thereafter, a number of estrogenic compounds were synthesized and used therapeutically, but the mechanisms of estrogen action remained obscure. However, in 1958 Elwood Jensen produced a major breakthrough when he used a radioactive marker to demonstrate that only estrogen-responsive tissues were able to concentrate injected estrogen from the blood, suggesting the existence of estrogen-binding components, which were called “estrogen receptors (ERs).” Further...