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Estradiol (17-beta estradiol) (also oestradiol) is a sex hormone. Labelled the "female" hormone but also present in males it represents the major estrogen in humans. Critical for sexual functioning, estradiol also supports bone growth.


Estradiol, like other sex steroids, is derived from cholesterol. After side chain cleavage and either utilizing the delta-5 pathway or the delta-4 pathway androstenedione is the key intermediary. Androstendione is either converted to testosterone which in turn undergoes aromatization to estradiol, or, alternatively, androstendione is aromatized to estrone which is converted to estradiol.

Estradiol Drug
During the reproductive years most estradiol in women is produced by the granulosa cells of the ovaries by aromatization of testosterone from the theca cells, or conversion of estrone to estradiol. Smaller amounts of estradiol are also produced by the adrenal cortex. In men, the testes produce some estradiol. An additional source of estradiol in both sexes is peripheral aromatization of testosterone to estradiol. Particularly fat cells are active to convert precursors to estradiol, and will continue to do so even after the menopause.

Mechanism of action
Estradiol enters cells freely and interacts with a target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estradiol upon the target cell.

Estradiol has many functions, among them are:

Breast development and maintenance
Adding fat to breasts, hips, thighs during puberty
Improving bone strength and density
Accelerating bone maturation and bringing epiphyses to closure, completing growth
Growth of the uterus
Development of the endometrial lining to a thickness necessary to support pregnancy and menstruation
Thinning of cervical mucus at ovulation
Promoting and maintaining vaginal mucosal thickness and secretions
Serving as the primary feedback to the brain of sex hormone levels in both males and females.
Participating in triggering ovulation
Preservation of egg cells
Enabling spermatogenesis
Effect on lipids
Vascular effects
Cerebral effects

Role in sexual differentiation
One of the fascinating twists to mammalian sexual differentiation is that estradiol is one of the two active metabolites of testosterone in males (the other being dihydrotestosterone). Estradiol cannot be transferred readily from the circulation into the brain. Since fetuses of both sexes are exposed to similarly high levels of maternal estradiol, it can play little role in prenatal sexual differentiation. However, testosterone enters the central nervous system more freely and significant amounts are aromatized to estradiol within the brain of most male mammals, including humans. There is now much evidence that the programming of adult male sexual behavior in "lower mammals," (such as mounting rather than lordosis behavior), is largely dependent on estradiol produced in the central nervous system during prenatal life and early infancy from testosterone. We do not yet know whether this process plays a minimal or significant part in human sexual behaviors.

Hormone replacement therapy
In the event that levels of estradiol in a woman's blood are low (possibly due to menopause or oophorectomy), a hormone replacement therapy may be prescribed, including drugs such as Premarin, Estrofem, or Estrace.

This may also be used in the case of Transsexuals.

Blocking estrogens
Inducing a state of hypoestrogenism may be beneficial in certain situations where estrogens are contributing to unwanted effects, e.g, certain forms of breast cancer, gynecomastia, and premature closure of epiphyses. Estrogen levels can be reduced by inhibiting production using gonadotropin- releasing factor agonists (GnRH agonists) or blocking the aromatase enzyme using an aromatase inhibitor, or estrogen effects can be reduced with estrogen antagonists such as tamoxifen. Flaxseed is known to reduce estradiol (Chevallier, 2000).

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