Estradiol-17β (E2) steroid hormone is produced mainly in the ovary, stimulates proliferation of the uterine endometrium, induces the LH surge for ovulation, and inhibits the pituitary hormone release via negative feedback. E2 is also produced in the testis but in low concentrations. E2 is converted from testosterone by aromatase or from estrone by 17β-hydroxysteroid dehydrogenase in the granulosa cell and luteal cell of the ovary, Leydig cells of the testis, adrenal gland, placenta, brain, and adipose tissue. The estrogen receptors (ERs) for E2 are ERα and ERβ in mammals, avians, reptilians, amphibians, and ancient fish species. ERα is considered to have a pivotal role because ERα knockout (ERα KO) female mice are sterile due to the inefficient levels of gonadotropins and lack of sensitivity to estradiol treatment, and ERα KO male mice are also sterile. ERβ KO female mice are fertile but exhibit reduced ovulation rates, while ERβ KO male mice exhibit fertility.