Estriol (E3), also spelled oestriol, is a steroid, a weak estrogen, and a minor female sex hormone. It is one of three major endogenous estrogens, the others being estradiol and estrone. However, during pregnancy, estriol is synthesized in very high quantities by the placenta and is the most produced estrogen in the body by far, although circulating levels of estriol are similar to those of other estrogens due to a relatively high rate of metabolism and excretion. It is a far less potent estrogen than is estradiol, and as such is a relatively weak estrogen. According to one in vitro study, the relative binding affinity (RBA) of estriol for the human ERα and ERβ was 11.3% and 17.6% of that of estradiol, respectively, and the relative transactivational capacity of estriol at the ERα and ERβ was 10.6% and 16.6% of that of estradiol, respectively. suggesting that unlike estradiol and estrone, estriol may have preferential affinity for ERβ. It is notable that unlike estriol, estrone can be metabolized into estradiol, and most of its potency in vivo is in fact actually due to conversion into estradiol. 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. In essence, it follows the pathway from dehydroepiandrosterone or DHEA (at left), but with a modified DHEA with an additional OH-group.]]
Biosynthesis
In non-pregnant women
In women who are not pregnant estriol is produced in only very small quantities, and circulating levels are barely detectable. and is instead derived mainly if not exclusively from 16α-hydroxylation of estradiol and estrone by cytochrome P450 enzymes (e.g., CYP3A4) mainly in the liver. Estriol is cleared from the circulation rapidly in non-pregnant women, and so circulating levels are very low, but concentrations of estriol in the urine are relatively high. At term, the daily production of estriol by the placenta is 35 to 45 mg, 16α-OH-DHEA-S is then taken up by the placenta. which is subsequently converted into estriol by 17β-hydroxysteroid dehydrogenase and then secreted predominantly into the maternal circulation. Approximately 90% of precursors in estriol formation originate from the fetus. with much lower binding affinity for this protein, relative to estradiol, and hence a greater fraction available for biological activity.
Metabolism
Estriol is metabolized via glucuronidation and sulfation. The metabolism and excretion of estriol in these animals closely resembled that which has been observed in humans.
Medical use
Estriol is used as a medication, primarily in hormone therapy for menopausal symptoms. The name estriol and the abbreviation E3 were derived from the chemical terms estrin (estra-1,3,5(10)-triene) and triol (three hydroxyl groups).
History
Estriol was discovered in 1930. It was isolated and purified from the urine of pregnant women by Marrian and colleagues. 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.