Estrogen or oestrogen is a category of
sex hormone responsible for the development and regulation of the female
reproductive system and
secondary sex characteristics.
There are three major
endogenous
Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell.
In contrast, exogenous substances and processes are those that originate from outside of an organism.
For example, es ...
estrogens that have estrogenic hormonal activity:
estrone (E1),
estradiol (E2), and
estriol (E3).
Estradiol, an
estrane, is the most potent and prevalent.
Another estrogen called
estetrol (E4) is produced only during pregnancy.
Estrogens are synthesized in all vertebrates
and some insects.
Their presence in both vertebrates and insects suggests that estrogenic sex hormones have an ancient evolutionary history. Quantitatively, estrogens circulate at lower levels than
androgens in both men and women.
While estrogen levels are significantly lower in males than in females, estrogens nevertheless have important physiological roles in males.
Like all
steroid hormones, estrogens readily
diffuse across the
cell membrane. Once inside the cell, they bind to and activate
estrogen receptors (ERs) which in turn
modulate the
expression of many
genes.
Additionally, estrogens bind to and activate rapid-signaling
membrane estrogen receptors (mERs),
such as
GPER (GPR30).
In addition to their role as natural hormones, estrogens are used as
medications, for instance in
menopausal hormone therapy,
hormonal birth control and
feminizing hormone therapy for
transgender women and
nonbinary people.
Synthetic and natural estrogens have been found in the environment and are referred to as
xenoestrogens. Estrogens are among the wide range of endocrine-disrupting compounds (EDCs) and can cause health issues and reproductive disfunction in both wildlife and humans.
Types and examples
The four major naturally occurring estrogens in women are
estrone (E1),
estradiol (E2),
estriol (E3), and
estetrol (E4). Estradiol(E2) is the predominant estrogen during reproductive years both in terms of absolute serum levels as well as in terms of estrogenic activity. During
menopause, estrone is the predominant circulating estrogen and during pregnancy estriol is the predominant circulating estrogen in terms of serum levels. Given by
subcutaneous injection
Subcutaneous administration is the insertion of medications beneath the skin either by injection or infusion.
A subcutaneous injection is administered as a bolus into the subcutis, the layer of skin directly below the dermis and epidermis, ...
in mice, estradiol is about 10-fold more potent than estrone and about 100-fold more potent than estriol.
Thus, estradiol is the most important estrogen in non-pregnant females who are between the
menarche
Menarche ( ; ) is the first menstrual cycle, or first menstrual bleeding, in female humans. From both social and medical perspectives, it is often considered the central event of female puberty, as it signals the possibility of fertility.
Gir ...
and menopause stages of life. However, during
pregnancy this role shifts to estriol, and in postmenopausal women estrone becomes the primary form of estrogen in the body. Another type of estrogen called
estetrol (E4) is produced only during pregnancy. All of the different forms of estrogen are synthesized from
androgens, specifically
testosterone and
androstenedione
Androstenedione, or 4-androstenedione (abbreviated as A4 or Δ4-dione), also known as androst-4-ene-3,17-dione, is an endogenous weak androgen steroid hormone and intermediate in the biosynthesis of estrone and of testosterone from dehydroepia ...
, by the
enzyme aromatase.
Minor endogenous estrogens, the biosyntheses of which do not involve
aromatase, include
27-hydroxycholesterol,
dehydroepiandrosterone (DHEA),
7-oxo-DHEA,
7α-hydroxy-DHEA,
16α-hydroxy-DHEA,
7β-hydroxyepiandrosterone,
androstenedione
Androstenedione, or 4-androstenedione (abbreviated as A4 or Δ4-dione), also known as androst-4-ene-3,17-dione, is an endogenous weak androgen steroid hormone and intermediate in the biosynthesis of estrone and of testosterone from dehydroepia ...
(A4),
androstenediol (A5),
3α-androstanediol, and
3β-androstanediol
3β-Androstanediol, also known as 5α-androstane-3β,17β-diol, and sometimes shortened in the literature to 3β-diol, is an endogenous steroid hormone and a metabolite of androgens like dehydroepiandrosterone (DHEA) and dihydrotestosterone (DHT). ...
.
Some estrogen metabolites, such as the
catechol estrogen
A catechol estrogen is a steroidal estrogen that contains catechol (1,2-dihydroxybenzene) within its structure. The catechol estrogens are endogenous metabolites of estradiol and estrone and include the following compounds:
* 2-Hydroxylated:
** ...
s
2-hydroxyestradiol,
2-hydroxyestrone,
4-hydroxyestradiol, and
4-hydroxyestrone, as well as
16α-hydroxyestrone, are also estrogens with varying degrees of activity.
The biological importance of these minor estrogens is not entirely clear.
Biological function

The actions of estrogen are mediated by the
estrogen receptor (ER), a dimeric nuclear protein that binds to DNA and controls
gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. The ...
. Like other steroid hormones, estrogen enters passively into the cell where it binds to and activates the estrogen receptor. The estrogen:ER complex binds to specific DNA sequences called a
hormone response element to activate the transcription of target genes (in a study using an estrogen-dependent breast cancer cell line as model, 89 such genes were identified).
Since estrogen enters all cells, its actions are dependent on the presence of the ER in the cell. The ER is expressed in specific tissues including the ovary, uterus and breast. The metabolic effects of estrogen in postmenopausal women have been linked to the genetic polymorphism of the ER.
While estrogens are present in both
men and
women, they are usually present at significantly higher levels in women of reproductive age. They promote the development of female
secondary sexual characteristics, such as
breasts, and are also involved in the thickening of the
endometrium
The endometrium is the inner epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer: the basal layer contains stem cells which regenerate the functional layer. The functional laye ...
and other aspects of regulating the menstrual cycle. In males, estrogen regulates certain functions of the
reproductive system important to the maturation of
sperm
Sperm is the male reproductive cell, or gamete, in anisogamous forms of sexual reproduction (forms in which there is a larger, female reproductive cell and a smaller, male one). Animals produce motile sperm with a tail known as a flagellum, whi ...
and may be necessary for a healthy
libido.
Overview of actions
* Structural
**
Anabolic: Increases
muscle mass
Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscle ...
and strength, speed of muscle regeneration, and
bone density, increased sensitivity to exercise, protection against muscle damage, stronger
collagen
Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...
synthesis, increases the collagen content of
connective tissues,
tendons, and
ligament
A ligament is the fibrous connective tissue that connects bones to other bones. It is also known as ''articular ligament'', ''articular larua'', ''fibrous ligament'', or ''true ligament''. Other ligaments in the body include the:
* Peritoneal li ...
s, but also decreases stiffness of
tendons and
ligament
A ligament is the fibrous connective tissue that connects bones to other bones. It is also known as ''articular ligament'', ''articular larua'', ''fibrous ligament'', or ''true ligament''. Other ligaments in the body include the:
* Peritoneal li ...
s (especially during
menstruation
Menstruation (also known as a period, among other colloquial terms) is the regular discharge of blood and mucosal tissue from the inner lining of the uterus through the vagina. The menstrual cycle is characterized by the rise and fall of hor ...
). Decreased stiffness of tendons gives women much lower predisposition to muscle strains but soft ligaments are much more prone to injuries (
ACL tears are 2-8x more common among women than men).
** Anti-inflammatory properties
** Mediate formation of female
secondary sex characteristics
** Accelerate
metabolism
** Increased
fat storage in some body parts such as breasts, buttocks, and legs but decreased abdominal and
visceral fat (androgenic obesity).
Estradiol also regulates energy expenditure, body weight
homeostasis, and seems to have much stronger anti-obesity effects than testosterone in general.
* Women tend to have lower base strength but on average have about the same increases of muscle mass in responses to resistance training as men and far faster relative increases in strength.
** Stimulate
endometrial growth
** Increase
uterine growth
** Increase
vaginal lubrication
** Thicken the
vaginal wall
** Maintenance of vessel and skin
** Reduce
bone resorption, increase bone formation
*
Protein synthesis
** Increase
hepatic production
The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...
of
binding proteins
*
Coagulation
** Increase circulating level of
factors 2,
7,
9,
10,
plasminogen
** Decrease
antithrombin III
** Increase
platelet adhesiveness
** Increase
vWF (estrogen ->
Angiotensin II
Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adre ...
->
Vasopressin)
** Increase
PAI-1 and
PAI-2 also through Angiotensin II
*
Lipid
** Increase
HDL,
triglyceride
** Decrease
LDL, fat deposition
* Fluid balance
** Salt (
sodium) and water retention
** Increase
cortisol
Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone.
It is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal cortex in the adrenal gland ...
,
SHBG
*
Gastrointestinal tract
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organ (biology), organs of the digestive syste ...
** Reduce bowel motility
** Increase
cholesterol in
bile
Bile (from Latin ''bilis''), or gall, is a dark-green-to-yellowish-brown fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is produced continuously by the liver (liver bile ...
*
Melanin
** Increase
pheomelanin, reduce
eumelanin
Melanin (; from el, μέλας, melas, black, dark) is a broad term for a group of natural pigments found in most organisms. Eumelanin is produced through a multistage chemical process known as melanogenesis, where the oxidation of the amin ...
* Cancer
** Support hormone-sensitive breast cancers (see section below)
*
Lung function
** Promotes lung function by supporting
alveoli Alveolus (; pl. alveoli, adj. alveolar) is a general anatomical term for a concave cavity or pit.
Uses in anatomy and zoology
* Pulmonary alveolus, an air sac in the lungs
** Alveolar cell or pneumocyte
** Alveolar duct
** Alveolar macrophage
* ...
(in rodents but probably in humans).
*
Uterus lining
** Estrogen together with
progesterone
Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the m ...
promotes and maintains the uterus lining in preparation for implantation of fertilized egg and maintenance of uterus function during gestation period, also upregulates
oxytocin
Oxytocin (Oxt or OT) is a peptide hormone and neuropeptide normally produced in the hypothalamus and released by the posterior pituitary. It plays a role in social bonding, reproduction, childbirth, and the period after childbirth. Oxytocin ...
receptor in myometrium
*
Ovulation
** Surge in estrogen level induces the release of
luteinizing hormone, which then triggers ovulation by releasing the egg from the
Graafian follicle in the
ovary
The ovary is an organ in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus, where it may become fertilized by a sperm. There is an ovary () found on each side of the body. ...
.
*
Sexual behavior
** Estrogen is required for female mammals to engage in
lordosis behavior during
estrus (when animals are "in heat").
This behavior is required for sexual receptivity in these mammals and is regulated by the
ventromedial nucleus of the
hypothalamus.
**
Sex drive is dependent on
androgen levels
only in the presence of estrogen, but without estrogen, free testosterone level actually decreases sexual desire (instead of increases sex drive), as demonstrated for those women who have
hypoactive sexual desire disorder, and the sexual desire in these women can be restored by administration of estrogen (using oral contraceptive).
Female pubertal development
Estrogens are responsible for the development of female
secondary sexual characteristics during
puberty, including
breast development, widening of the
hip
In vertebrate anatomy, hip (or "coxa"Latin ''coxa'' was used by Celsus in the sense "hip", but by Pliny the Elder in the sense "hip bone" (Diab, p 77) in medical terminology) refers to either an anatomical region or a joint.
The hip region is ...
s, and female
fat distribution. Conversely,
androgens are responsible for
pubic and
body hair
Body hair, or androgenic hair, is the terminal hair that develops on the human body during and after puberty. It is differentiated from the head hair and less visible vellus hair, which is much finer and lighter in color. The growth of androge ...
growth
Growth may refer to:
Biology
* Auxology, the study of all aspects of human physical growth
* Bacterial growth
* Cell growth
* Growth hormone, a peptide hormone that stimulates growth
* Human development (biology)
* Plant growth
* Secondary growth ...
, as well as
acne and
axillary odor.
Breast development
Estrogen, in conjunction with
growth hormone (GH) and its secretory product
insulin-like growth factor 1 (IGF-1), is critical in mediating breast development during
puberty, as well as breast maturation during
pregnancy in preparation of
lactation and
breastfeeding.
Estrogen is primarily and directly responsible for inducing the ductal component of breast development,
as well as for causing
fat deposition
Adipose tissue, body fat, or simply fat is a loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular en ...
and
connective tissue
Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tiss ...
growth.
It is also indirectly involved in the lobuloalveolar component, by increasing
progesterone receptor
The progesterone receptor (PR), also known as NR3C3 or nuclear receptor subfamily 3, group C, member 3, is a protein found inside cells. It is activated by the steroid hormone progesterone.
In humans, PR is encoded by a single ''PGR'' gene resid ...
expression in the breasts
and by inducing the secretion of
prolactin.
Allowed for by estrogen,
progesterone
Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the m ...
and prolactin work together to complete lobuloalveolar development during pregnancy.
Androgens such as testosterone powerfully oppose estrogen action in the breasts, such as by reducing
estrogen receptor expression in them.
Female reproductive system
Estrogens are responsible for maturation and maintenance of the
vagina and
uterus, and are also involved in
ovarian function, such as maturation of
ovarian follicles. In addition, estrogens play an important role in regulation of
gonadotropin secretion 440px
Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical ...
. For these reasons, estrogens are required for female
fertility.
Neuroprotection and DNA repair
Estrogen regulated
DNA repair mechanisms in the
brain have neuroprotective effects. Estrogen regulates the
transcription of DNA
base excision repair genes as well as the translocation of the base excision repair enzymes between different subcellular compartments.
Brain and behavior
Sex drive
Estrogens are involved in
libido (sex drive) in both women and men.
Cognition
Verbal memory scores are frequently used as one measure of higher level
cognition
Cognition refers to "the mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception, attention, thought, ...
. These scores vary in direct proportion to estrogen levels throughout the menstrual cycle, pregnancy, and menopause. Furthermore, estrogens when administered shortly after natural or surgical menopause prevents decreases in verbal memory. In contrast, estrogens have little effect on verbal memory if first administered years after menopause.
Estrogens also have positive influences on other measures of cognitive function.
However the effect of estrogens on cognition is not uniformly favorable and is dependent on the timing of the dose and the type of cognitive skill being measured.
The protective effects of estrogens on cognition may be mediated by estrogen's anti-inflammatory effects in the brain.
Studies have also shown that the Met allele gene and level of estrogen mediates the efficiency of
prefrontal cortex dependent working memory tasks. Researchers have urged for further research to illuminate the role of estrogen and its potential for improvement on cognitive function.
Mental health
Estrogen is considered to play a significant role in women's
mental health. Sudden estrogen withdrawal, fluctuating estrogen, and
periods of sustained low estrogen levels correlate with a significant lowering of mood. Clinical recovery from
postpartum,
perimenopause, and
postmenopause
Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...
depression has been shown to be effective after levels of estrogen were stabilized and/or restored.
Menstrual exacerbation (including menstrual psychosis) is typically triggered by low estrogen levels, and is often mistaken for
premenstrual dysphoric disorder.
Compulsions in male lab mice, such as those in obsessive-compulsive disorder (OCD), may be caused by low estrogen levels. When estrogen levels were raised through the increased activity of the enzyme
aromatase in male lab mice, OCD rituals were dramatically decreased.
Hypothalamic
The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamus i ...
protein levels in the gene
COMT are enhanced by increasing estrogen levels which are believed to return mice that displayed OCD rituals to normal activity. Aromatase deficiency is ultimately suspected which is involved in the synthesis of estrogen in humans and has therapeutic implications in humans having obsessive-compulsive disorder.
Local application of estrogen in the rat hippocampus has been shown to inhibit the re-uptake of
serotonin
Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...
. Contrarily, local application of estrogen has been shown to block the ability of
fluvoxamine to slow serotonin clearance, suggesting that the same pathways which are involved in SSRI efficacy may also be affected by components of local estrogen signaling pathways.
Parenthood
Studies have also found that fathers had lower levels of cortisol and testosterone but higher levels of estrogen (estradiol) than did non-fathers.
Binge eating
Estrogen may play a role in suppressing
binge eating. Hormone replacement therapy using estrogen may be a possible treatment for binge eating behaviors in females. Estrogen replacement has been shown to suppress binge eating behaviors in female mice.
The mechanism by which estrogen replacement inhibits binge-like eating involves the replacement of
serotonin
Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...
(5-HT) neurons. Women exhibiting binge eating behaviors are found to have increased brain uptake of neuron 5-HT, and therefore less of the neurotransmitter serotonin in the cerebrospinal fluid.
Estrogen works to activate 5-HT neurons, leading to suppression of binge like eating behaviors.
It is also suggested that there is an interaction between hormone levels and eating at different points in the female
menstrual cycle
The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that make pregnancy possible. The ovarian cycle controls the production and release of eggs a ...
. Research has predicted increased emotional eating during hormonal flux, which is characterized by high
progesterone
Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the m ...
and
estradiol levels that occur during the mid-
luteal phase. It is hypothesized that these changes occur due to brain changes across the menstrual cycle that are likely a genomic effect of hormones. These effects produce menstrual cycle changes, which result in hormone release leading to behavioral changes, notably binge and emotional eating. These occur especially prominently among women who are genetically vulnerable to binge eating phenotypes.
Binge eating is associated with decreased estradiol and increased progesterone.
Klump et al.
Progesterone may moderate the effects of low estradiol (such as during dysregulated eating behavior), but that this may only be true in women who have had clinically diagnosed binge episodes (BEs). Dysregulated eating is more strongly associated with such ovarian hormones in women with BEs than in women without BEs.
The implantation of 17β-estradiol pellets in ovariectomized mice significantly reduced binge eating behaviors and injections of GLP-1 in ovariectomized mice decreased binge-eating behaviors.
The associations between binge eating, menstrual-cycle phase and ovarian hormones correlated.
Masculinization in rodents
In rodents, estrogens (which are locally aromatized from androgens in the brain) play an important role in psychosexual differentiation, for example, by masculinizing territorial behavior;
the same is not true in humans.
In humans, the masculinizing effects of prenatal androgens on behavior (and other tissues, with the possible exception of effects on bone) appear to act exclusively through the androgen receptor.
Consequently, the utility of rodent models for studying human psychosexual differentiation has been questioned.
Skeletal system
Estrogens are responsible for both the pubertal growth spurt, which causes an acceleration in linear growth, and
epiphyseal closure
The epiphyseal plate (or epiphysial plate, physis, or growth plate) is a hyaline cartilage plate in the metaphysis at each end of a long bone. It is the part of a long bone where new bone growth takes place; that is, the whole bone is alive, with ...
, which limits
height and
limb length, in both females and males. In addition, estrogens are responsible for bone maturation and maintenance of
bone mineral density
Bone density, or bone mineral density, is the amount of bone mineral in bone tissue. The concept is of mass of mineral per volume of bone (relating to density in the physics sense), although clinically it is measured by proxy according to optica ...
throughout life. Due to hypoestrogenism, the risk of
osteoporosis
Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone ...
increases during
menopause.
Cardiovascular system
Women are less impacted by heart disease due to vasculo-protective action of estrogen which helps in preventing atherosclerosis.
It also helps in maintaining the delicate balance between fighting infections and protecting arteries from damage thus lowering the risk of cardiovascular disease.
During
pregnancy, high levels of estrogens increase
coagulation and the risk of
venous thromboembolism. Estrogen has been shown to upregulate the
peptide hormone adropin.
Immune system
Estrogen has
anti-inflammatory properties and helps in mobilization of polymorphonuclear white blood cells or
neutrophils.
Associated conditions
Researchers have implicated estrogens in various
estrogen-dependent conditions, such as ER-positive
breast cancer, as well as a number of
genetic condition
A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...
s involving estrogen signaling or metabolism, such as
estrogen insensitivity syndrome,
aromatase deficiency
Aromatase deficiency is an exceedingly rare condition characterized by extremely low levels or complete absence of the enzyme aromatase activity in the body. It is an autosomal recessive disease resulting from various mutations of gene CPY19 (P450 ...
, and
aromatase excess syndrome.
High estrogen can amplify
stress-hormone responses in
stressful situations.
Biochemistry
Biosynthesis

Estrogens, in females, are produced primarily by the
ovaries, and during pregnancy, the
placenta.
Follicle-stimulating hormone
Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, pubertal maturation, an ...
(FSH) stimulates the ovarian production of estrogens by the
granulosa cells of the
ovarian follicles and
corpora lutea. Some estrogens are also produced in smaller amounts by other tissues such as the
liver,
pancreas,
bone,
adrenal glands,
skin,
brain,
adipose tissue,
and the
breasts. These secondary sources of estrogens are especially important in postmenopausal women.
The pathway of estrogen biosynthesis in extragonadal tissues is different. These tissues are not able to synthesize C19 steroids, and therefore depend on C19 supplies from other tissues
and the level of aromatase.
In females, synthesis of estrogens starts in
theca interna cells in the ovary, by the synthesis of
androstenedione
Androstenedione, or 4-androstenedione (abbreviated as A4 or Δ4-dione), also known as androst-4-ene-3,17-dione, is an endogenous weak androgen steroid hormone and intermediate in the biosynthesis of estrone and of testosterone from dehydroepia ...
from
cholesterol. Androstenedione is a substance of weak androgenic activity which serves predominantly as a
precursor for more potent androgens such as testosterone as well as estrogen. This compound crosses the
basal membrane into the surrounding granulosa cells, where it is converted either immediately into estrone, or into testosterone and then estradiol in an additional step. The conversion of androstenedione to testosterone is catalyzed by
17β-hydroxysteroid dehydrogenase
A hydroxysteroid is a molecule derived from a steroid with a hydrogen replaced with a hydroxy group. When the hydroxy group is specifically at the C3 position, hydroxysteroids are referred to as sterols, with an example being cholesterol.
See ...
(17β-HSD), whereas the conversion of androstenedione and testosterone into estrone and estradiol, respectively is catalyzed by aromatase, enzymes which are both expressed in granulosa cells. In contrast, granulosa cells lack
17α-hydroxylase
Cytochrome P450 17A1 (steroid 17α-monooxygenase, 17α-hydroxylase, 17-alpha-hydroxylase, 17,20-lyase, 17,20-desmolase) is an enzyme of the hydroxylase type that in humans is encoded by the ''CYP17A1'' gene on chromosome 10. It is ubiquitously expr ...
and
17,20-lyase
Cytochrome P450 17A1 (steroid 17α-monooxygenase, 17α-hydroxylase, 17-alpha-hydroxylase, 17,20-lyase, 17,20-desmolase) is an enzyme of the hydroxylase type that in humans is encoded by the ''CYP17A1'' gene on chromosome 10. It is ubiquitously exp ...
, whereas theca cells express these enzymes and 17β-HSD but lack aromatase. Hence, both granulosa and theca cells are essential for the production of estrogen in the ovaries.
Estrogen levels vary through the
menstrual cycle
The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that make pregnancy possible. The ovarian cycle controls the production and release of eggs a ...
, with levels highest near the end of the
follicular phase just before
ovulation.
Note that in males, estrogen is also produced by the
Sertoli cells when FSH binds to their FSH receptors.
Distribution
Estrogens are
plasma protein bound
Plasma protein binding refers to the degree to which medications attach to proteins within the blood. A drug's efficiency may be affected by the degree to which it binds. The less bound a drug is, the more efficiently it can traverse or diffuse th ...
to
albumin and/or
sex hormone-binding globulin in the circulation.
Metabolism
Estrogens are
metabolized via
hydroxylation
In chemistry, hydroxylation can refer to:
*(i) most commonly, hydroxylation describes a chemical process that introduces a hydroxyl group () into an organic compound.
*(ii) the ''degree of hydroxylation'' refers to the number of OH groups in a ...
by
cytochrome P450
Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...
enzymes such as
CYP1A1 and
CYP3A4
Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...
and via
conjugation by
estrogen sulfotransferase
Estrone sulfotransferase (EST) (), also known as estrogen sulfotransferase, is an enzyme that catalyzes the transformation of an unconjugated estrogen like estrone into a sulfated estrogen like estrone sulfate. It is a steroid sulfotransferase ...
s (
sulfation) and
UDP-glucuronyltransferases (
glucuronidation). In addition, estradiol is
dehydrogenated
In chemistry, dehydrogenation is a chemical reaction that involves the removal of hydrogen, usually from an organic molecule. It is the reverse of hydrogenation. Dehydrogenation is important, both as a useful reaction and a serious problem. At ...
by
17β-hydroxysteroid dehydrogenase
A hydroxysteroid is a molecule derived from a steroid with a hydrogen replaced with a hydroxy group. When the hydroxy group is specifically at the C3 position, hydroxysteroids are referred to as sterols, with an example being cholesterol.
See ...
into the much less potent estrogen estrone. These reactions occur primarily in the
liver, but also in other
tissues.
Excretion
Estrogens are
excreted primarily by the
kidneys as
conjugates via the
urine.
Medical use
Estrogens are used as
medications, mainly in
hormonal contraception
Hormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The origin ...
,
hormone replacement therapy,
and to treat gender dysphoria in
transgender women and other
transfeminine individuals as part of feminizing hormone therapy.
Chemistry
The estrogen steroid hormones are
estrane steroid
A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...
s.
History
In 1929,
Adolf Butenandt and
Edward Adelbert Doisy independently isolated and purified estrone, the first estrogen to be discovered.
Then, estriol and estradiol were discovered in 1930 and 1933, respectively. Shortly following their discovery, estrogens, both natural and synthetic, were introduced for medical use. Examples include
estriol glucuronide (
Emmenin,
Progynon),
estradiol benzoate,
conjugated estrogens (
Premarin),
diethylstilbestrol, and
ethinylestradiol.
The word estrogen derives from
Ancient Greek. It is derived from "oestros"
(a periodic state of sexual activity in female mammals), and genos (generating).
It was first published in the early 1920s and referenced as "oestrin". With the years, American English adapted the spelling of estrogen to fit with its phonetic pronunciation. Nevertheless, both estrogen and oestrogen are used nowadays, yet some still wish to maintain its original spelling as it reflects the origin of the word.
Society and culture
Etymology
The name ''estrogen'' is derived from the
Greek (), literally meaning "verve" or "inspiration" but figuratively sexual passion or desire, and the suffix ''
-gen'', meaning "producer of".
Environment
A range of synthetic and natural substances that possess estrogenic activity have been identified in the
environment and are referred to
xenoestrogens.
* Synthetic substances such as
bisphenol A
Bisphenol A (BPA) is a chemical compound primarily used in the manufacturing of various plastics. It is a colourless solid which is soluble in most common organic solvents, but has very poor solubility in water. BPA is produced on an industrial s ...
as well as
metalloestrogen
Metalloestrogens are a class of inorganic xenoestrogens which can affect the gene expression of human cells responding to estrogen. Effects are related to the physiologic function of estrogen because metalloestrogens have shown affinity for estroge ...
s (e.g.,
cadmium).
* Plant products with estrogenic activity are called
phytoestrogens (e.g.,
coumestrol,
daidzein,
genistein,
miroestrol
Miroestrol is a phytoestrogen, a plant-derived chemical that mimics the biological activity of the hormone estrogen. Miroestrol was first reportedly isolated from the Thai herb ''Pueraria mirifica'' in 1960 and thought to be responsible for the ...
).
* Those produced by fungi are known as
mycoestrogens (e.g.,
zearalenone).
Estrogens are among the wide range of
endocrine-disrupting compounds (EDCs) because they have high estrogenic potency. When an EDC makes its way into the environment, it may cause male reproductive dysfunction to wildlife and humans.
The estrogen excreted from farm animals makes its way into fresh water systems.
During the germination period of reproduction the fish are exposed to low levels of estrogen which may cause reproductive dysfunction to male fish.
Cosmetics
Some hair
shampoos on the market include estrogens and placental extracts; others contain
phytoestrogens. In 1998, there were case reports of four prepubescent African-American girls developing breasts after exposure to these shampoos.
In 1993, the FDA determined that not all
over-the-counter topically applied hormone-containing drug products for human use are
generally recognized as safe and effective and are misbranded. An accompanying proposed rule deals with cosmetics, concluding that any use of natural estrogens in a cosmetic product makes the product an unapproved new drug and that any cosmetic using the term "hormone" in the text of its labeling or in its ingredient statement makes an implied drug claim, subjecting such a product to regulatory action.
In addition to being considered misbranded drugs, products claiming to contain placental extract may also be deemed to be misbranded cosmetics if the extract has been prepared from placentas from which the hormones and other biologically active substances have been removed and the extracted substance consists principally of protein. The FDA recommends that this substance be identified by a name other than "placental extract" and describing its composition more accurately because consumers associate the name "placental extract" with a therapeutic use of some biological activity.
See also
*
List of steroid abbreviations
*
Breastfeeding and fertility
References
External links
* Nussey and Whitehead:
Endocrinology, an integrated approach', Taylor and Francis 2001. Free online textbook.
{{Authority control
Phenols
Cyclopentanols
Antigonadotropins
Estranes
Fertility
Hepatotoxins
Hormones of the hypothalamus-pituitary-gonad axis
Hormones of the hypothalamic-pituitary-prolactin axis
Hormones of the ovary
Hormones of the pregnant female
Hormones of the testis
Human female endocrine system
Human hormones
Mammal female reproductive system
Prolactin releasers
Sex hormones
1929 in science
1929 in Germany
Sterols
Puberty