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Estradiol

From Academic Kids

Image:estradiol.png

Estradiol (17-beta estradiol) 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.

Contents

Synthesis

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.

Conversion of testosterone to estradiol: Missing image
Reaction-Testosterone-Estradiol.png
Image:Reaction-Testosterone-Estradiol.png

Production

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. This estrogen receptor is located in the nucleus of the target cell and regulates 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.

Effects

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.

Therapy

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™.

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.

See also

pl:Estradiol de:Estradiol

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