Estradiol is the most potent form of mammalian estrogenic steroids. Estradiol is produced in the ovaries. The ovary requires both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to produce sex steroids. LH stimulates the cells surrounding the follicle to produce progesterone and androgens. The androgens diffuse across the basement membrane to the granulosa cell layer, where, under the action of FSH, they are aromatized to estrogens, mainly estradiol. The ovary shows cyclical activity, unlike the testis that is maintained in a more or less constant state of activity. Hormone secretions vary according to the phase of the menstrual cycle. In the developing follicle LH receptors (LH-R) are only located on the thecal cells and FSH receptors (FSHR) on the granulosa cells. The dominant pre-ovulatory follicle develops LH-Rs on the granulosa cells prior to the LH surge. Thecal cells of the preovulatory follicle also develop the capacity to synthesize estradiol and this persists when the thecal cells become incorporated into the corpus luteum. After ovulation, the empty follicle is remodelled and plays an important role in the second half or luteal phase of the menstrual cycle. This phase is dominated by progesterone and, to a lesser extent, estradiol secretion by the corpus luteum. estradiol is also synthesized locally from cholesterol through testosterone in the hippocampus and acts rapidly to modulate neuronal synaptic plasticity. Localization of estrogen receptor alpha (ERalpha) in spines in addition to nuclei of principal neurons implies that synaptic ERalpha is responsible for rapid modulation of synaptic plasticity by endogenous estradiol. estradiol is a potent endogenous antioxidant which suppresses hepatic fibrosis in animal models, and attenuates induction of redox sensitive transcription factors, hepatocyte apoptosis and hepatic stellate cells activation by inhibiting a generation of reactive oxygen species in primary cultures. This suggests that the greater progression of hepatic fibrosis and hepatocellular carcinoma in men and postmenopausal women may be due, at least in part, to lower production of estradiol and a reduced response to the action of estradiol. estradiol has been reported to induce the production of interferon (INF)-gamma in lymphocytes, and augments an antigen-specific primary antibody response in human peripheral blood mononuclear cells. IFN-gamma is a potent cytokine with immunomodulatory and antiproliferative properties. Therefore, female subjects, particularly before menopause, may produce antibodies against hepatitis B virus e antigen and hepatitis B virus surface antigen at a higher frequency than males with chronic hepatitis B virus infection. The estradiol-Dihydrotestosterone model of prostate cancer (PC) proposes that the first step in the development of most PC and breast cancer (BC) occurs when aromatase converts testosterone to estradiol. (PMID: 17708600, 17678531, 17644764).