|Jmol 3D model||Interactive image|
|Molar mass||288.39 g·mol−1|
|G03CA04 (WHO) G03CC06 (WHO)|
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
|what is ?)(|
Estriol (E3), or oestriol, is one of the three main estrogens produced by the human body.
Estriol is only produced in significant amounts during pregnancy as it is made by the placenta from 16-hydroxydehydroepiandrosterone sulfate (16-OH DHEAS), an androgen steroid made in the fetal liver and adrenal glands.
The human placenta produces pregnenolone and progesterone from circulating cholesterol. Pregnenolone is converted in the fetal adrenal gland into dehydroepiandrosterone (DHEA), a C19 steroid, then subsequently sulfonated to dehydroepiandrosterone sulfate (DHEAS). DHEAS is converted to 16-OH DHEAS in the fetal liver. The placenta converts 16-OH DHEAS to estriol, and is the predominant site of estriol synthesis.
Mechanism of action
Similarly to estradiol and estrone, estriol binds to and acts as an agonist of both of the estrogen receptors (ER), ERα and ERβ. The affinities of estriol for the ERα and ERβ relative to those of estradiol are 14% and 21%, respectively. As such, unlike estradiol (and estrone), estriol has preferential affinity for ERβ. However, estriol is described as a relatively weak estrogen and has mixed agonist-antagonist activity at the ER; on its own, it is weakly estrogenic, but in the presence estradiol, it is antiestrogenic. Relative to estradiol, estriol has 80-fold lower estrogenic potency while estrone has 12-fold lower estrogenic potency. Estriol also acts as an antagonist of the GPER, where, conversely, estradiol acts as an agonist. Estradiol increases breast cancer cell growth via activation of the GPER (in addition to the ER), and estriol has been found to inhibit estradiol-induced proliferation of triple-negative breast cancer cells through blockade of the GPER.
Levels of estriol in non-pregnant women do not change much after menopause, and levels are not significantly different from levels in men. During pregnancy, estriol is the principle estrogen produced by the placenta. Its levels increase 1000-fold during pregnancy, while levels of estradiol and estrone each increase 100-fold. Estriol circulates at levels 10 to 20 times those of other estrogens during pregnancy. At term, the daily production of estriol by the placenta is 35 to 45 mg. Postpartum women continue to produce higher levels of estriol relative to nulliparous women following pregnancy.
Estriol can be a weak or strong estrogen depending on if it is given acutely or chronically when given to immature animals, but is an antagonist when given in combination with estradiol. Estriol may play a role in the development of breast cancer, but based on in vitro research, does appear to act as an antagonist to the GPER. Though estriol is used as part of the primarily North American phenomenon of bioidentical hormone replacement therapy, it is not approved for use by the FDA or Health Canada. Though initial research in the 1970s suggested it could be used therapeutically as an estrogen, subsequent research failed to confirm this hypothesis.
Use in screening
Estriol can be measured in maternal blood or urine and can be used as a marker of fetal health and wellbeing. DHEA-S is produced by the adrenal cortex of the fetus. This is converted to estriol by the placenta.
If levels of unconjugated estriol (uE3 or free estriol) are abnormally low in a pregnant woman, this may indicate chromosomal or congenital anomalies like Down syndrome or Edward's syndrome. It is included as part of the triple test & quadruple test for antenatal screening for fetal anomalies.
Because many pathological conditions in a pregnant woman can cause deviations in estriol levels, these screenings are often seen as less definitive of fetal-placental health than a nonstress test. Conditions which can create false positives and false negatives in estriol testing for fetal distress include preeclampsia, anemia, and impaired kidney function.
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