Estradiol

Estradiol is a powerful steroid hormone belonging to the estrogen group, and is often misleadingly called the "female hormone". It is a product of cholesterol metabolism (by way of testosterone) and is vital to the maintenance of fertility and secondary sex characteristics in females, as well as bone density in both sexes.

Estradiol

It is the primary estrogen in humans. Among its functions and effects:

• 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
• 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.

Most estradiol in women is produced by the granulosa cells of the ovaries by aromatization of testosterone from the theca cells. Smaller amounts of estradiol are also produced by the adrenal cortex. An additional source of estradiol in both sexes is peripheral aromatization of testosterone to estradiol.

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. In the event that levels of estradiol in a woman's blood are low (possibly due to menopause, oophorectomy, transsexuality, etc.), a hormone replacement therapy may be prescribed, including drugs such as Premarinâ„¢, Estrofemâ„¢, or Estraceâ„¢.

Synthesis

Estradiol is synthesized from the androgen testosterone. The conversion consists of the de-methylation of C-19 and the aromaticity of the 'A' ring.

Effects

Female reproduction

In the female estradiol act as a growth hormone for tissue of the reproductive organs, supporting the lining of the vagina, the cervical glands, the endometrium and the lining of the fallopian tubes. It enhances growth of the myometrium. Estradiol appears necessary to maintain oocytes in the ovary. During the menstrual cycle, estradiol that is produced by the growing follicle triggers via a positive feedback system the hypothalamic-pituitary events that lead to the LH surge, inducing ovulation. In the luteal phase estradiol , in conjunction with progesterone, prepares the endometrium for implantation. During pregnancy estradiol increases due to placental production. In baboons, blocking of estrogen production leads to pregnancy loss suggesting that estradiol has a role in the maintenance of pregnancy. Research is investigating the role of estrogens in the process of initiation of labor.

Sexual development

The development of secondary sexual characteristics in women is driven by estrogens, specifically estradiol. These changes are initiated at the time of puberty, most enhanced during the reproductive years, and become less pronounced with declining estradiol support after the menopause. Thus, estradiol enhances breast development, and responsible for changes in the body contour affecting bones, joints, fat deposition. Fat structure and skin composition are modified by estradiol.

Male reproduction

The effect of estradiol (and estrogens) upon male reproduction is complex. Estradiol is produced in the Leydig cell of the testes. There is evidence that estradiol is to prevent apoptosis (one of the main types of programmed cell death) of male germ cells. {Pentikäinen V, Erkkilä K, Suomalainen L, Parvinen M, Dunkel L. Estradiol Acts as a Germ Cell Survival Factor in the Human Testis in vitro. The Journal of Clinical Endocrinology & Metabolism 2006;85:2057-67 PMID 10843196}

Several studies have noted that sperm counts have been declining in many parts of the world and it has been postulated that this may be related to estrogen exposure in the environment.

Bone

There is ample evidence that estradiol has a profound effect on bone. Individuals without estradiol (or other estrogens) will become tall and eunuchoid as epiphysieal closure is delayed or may not take place. Bone structure is affected resulting in early osteopenia and osteoporosis. {Carani C, Qin K, Simoni M, Faustini-Fustini M, Serpente S, Boyd J, Korach KS, Simpson ER. Effect of Testosterone and Estradiol in a Man with Aromatase Deficiency. New England Journal of Medicine Volume 337:91-95 July 10, 1997 PMID 9211678} Also, women who past the menopause experience an accelerated loss of bone mass due to a relative estrogen deficiency.

Liver

Estradiol has complex affects on the liver. It can lead to cholestasis, a liver disease. It affects the production of multiple proteins including lipoproteins, binding proteins, and proteins responsible for blood clotting (see blood clots).

Brain

Estrogens can be produced in the brain from steroid precursors. As an antioxidant, they have been found to have a neuroprotective function. {Behl C, Widmann M, Trapp T, Holsboer F. 17-beta estradiol protects neurons from oxidative stress-induced cell death in vitro. Biochem Biophys Res Commun. 1995 Nov 13;216(2):473-82. PMID 7488136}

The positive and negative feedback loop of the menstrual cycle involve ovarian estradiol as the link to the hypothalamic-pituitary system to regulate gonadotropins (protein hormones).

Blood vessels

Estrogen affects certain blood vessels. Improvement in arterial blood flow has demonstrated in coronary arteries. {Collins P, Rosano GM, Sarrel PM, Ulrich L, Adamopoulos S, Beale CM, McNeill JG, Poole-Wilson PA. 17 beta-Estradiol attenuates acetylcholine-induced coronary arterial constriction in women but not men with coronary heart disease. Circulation. 1995 Jul 1;92(1):24-30 PMID 7788912}

Oncogene

Estrogen is considered an oncogene as its supports certain cancers, notably breast cancer and cancer of the uterine lining. In addition there are several benign gynecologic conditions that are dependent on estrogen such as endometriosis, leiomyomata uteri, and uterine bleeding.

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 - elevating the female genitals, so the male can more easily mate with the female), 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.

See Also

• estrogen insensitivity syndrome
• hormone replacement therapy (male-to-female)
• gender
• androgen

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