Biomarkers

Target: Estradiol

Estradiol (E2) is an estrogen steroid hormone and is the major female sex hormone. It is the most potent form of mammalian estrogenic steroids. Estradiol is produced in the ovaries, but also in other tissues including the testicles, the adrenal glands, fat, liver, the breasts, and the brain. Estradiol is produced in the body from cholesterol. The major pathway involves the formation of androstenedione, which is then converted by aromatase into estrone and is subsequently converted into estradiol. Estradiol is responsible for the development of female secondary sexual characteristics such as the breasts, widening of the hips, and a female-associated pattern of fat distribution and is important in the development and maintenance of female reproductive tissues such as the mammary glands, uterus, and vagina during puberty, adulthood, and pregnancy. It also has important effects in many other tissues including bone, fat, skin, liver, and the brain. Though estradiol levels in males are much lower than in females, estradiol has important roles in males as well. Upon menopause in females, production of estrogens by the ovaries stops and estradiol levels decrease to very low levels. In addition to its role as a natural hormone, estradiol is used as a medication, for instance in menopausal hormone therapy. 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).↵