Estriol
Encyclopedia
Estriol is one of the three main estrogen
s produced by the human body.
Estriol (E3) 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 gland
s.
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.
, and levels are not significantly different from levels in men.
(MS), estriol reduces the disease's symptoms noticeably, according to researchers at UCLA's Geffen Medical School.
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 G-protein coupled estrogen receptor
. Though estriol is used as part of the primarily North America
n 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.
of the fetus. This is converted to estriol by the fetal liver.
If levels of "unconjugated 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 non-stress testing. Conditions which can create false positives and false negatives in estriol testing for fetal distress include preeclampsia, anemia
and impaired kidney function.
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
s produced by the human body.
Synthesis
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
as it is made by the placenta from 16-Hydroxydehydroepiandrosterone sulfate (16-OH DHEAS), an androgen steroid made in the fetal liver and adrenal gland
Adrenal gland
In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...
s.
The human placenta produces pregnenolone
Pregnenolone
Pregnenolone is a steroid hormone involved in the steroidogenesis of progesterone, mineralocorticoids, glucocorticoids, androgens, and estrogens. As such it is a prohormone. Pregnenolone sulfate is a GABAA antagonist and increases neurogenesis in the hippocampus.-Chemistry:Like other steroids,...
and progesterone
Progesterone
Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
from circulating cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
. Pregnenolone is converted in the fetal adrenal gland into dehydroepiandrosterone
Dehydroepiandrosterone
5-Dehydroepiandrosterone is a 19-carbon endogenous steroid hormone. It is the major secretory steroidal product of the adrenal glands and is also produced by the gonads and the brain. DHEA is the most abundant circulating steroid in humans....
(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.
Levels
Levels of estriol in non-pregnant women do not change much after menopauseMenopause
Menopause is a term used to describe the permanent cessation of the primary functions of the human ovaries: the ripening and release of ova and the release of hormones that cause both the creation of the uterine lining and the subsequent shedding of the uterine lining...
, and levels are not significantly different from levels in men.
Therapeutic use
In pregnant women with multiple sclerosisMultiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
(MS), estriol reduces the disease's symptoms noticeably, according to researchers at UCLA's Geffen Medical School.
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
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
when given in combination with estradiol
Estradiol
Estradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
. Estriol may play a role in the development of breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
, but based on in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
research does appear to act as an antagonist to the G-protein coupled estrogen receptor
GPR30
G-protein coupled estrogen receptor 1 also known as the membrane estrogen receptor or G-protein coupled receptor 30 is a G protein-coupled receptor that in humans is encoded by the GPER gene...
. Though estriol is used as part of the primarily North America
North America
North America is a continent wholly within the Northern Hemisphere and almost wholly within the Western Hemisphere. It is also considered a northern subcontinent of the Americas...
n phenomenon of bioidentical hormone replacement therapy
Bioidentical hormone replacement therapy
Bioidentical hormone replacement therapy , also known as bioidentical hormone therapy or natural hormone therapy, is a poorly-defined term referring to the use of hormones that are identical, on a molecular level, with endogenous hormones in hormone replacement therapy...
, it is not approved for use by the FDA or Health Canada
Health Canada
Health Canada is the department of the government of Canada with responsibility for national public health.The current Minister of Health is Leona Aglukkaq, a Conservative Member of Parliament appointed to the position by Prime Minister Stephen Harper.-Branches, regions and agencies: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 cortexAdrenal cortex
Situated along the perimeter of the adrenal gland, the adrenal cortex mediates the stress response through the production of mineralocorticoids and glucocorticoids, including aldosterone and cortisol respectively. It is also a secondary site of androgen synthesis.-Layers:Notably, the reticularis in...
of the fetus. This is converted to estriol by the fetal liver.
If levels of "unconjugated estriol" are abnormally low in a pregnant woman, this may indicate chromosomal or congenital anomalies like Down syndrome
Down syndrome
Down syndrome, or Down's syndrome, trisomy 21, is a chromosomal condition caused by the presence of all or part of an extra 21st chromosome. It is named after John Langdon Down, the British physician who described the syndrome in 1866. The condition was clinically described earlier in the 19th...
or Edward's syndrome. It is included as part of the triple test
Triple test
The triple test, also called triple screen, the Kettering test or the Bart's test, is an investigation performed during pregnancy in the second trimester to classify a patient as either high-risk or low-risk for chromosomal abnormalities .The term "multiple-marker screening test" is sometimes used...
& 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 non-stress testing. Conditions which can create false positives and false negatives in estriol testing for fetal distress include preeclampsia, anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
and impaired kidney function.