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Estrogens or oestrogens, are a class of natural or synthetic
sex hormone Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormone A steroid hormone is a steroid , hypothetical a steroid with 32 carbon atoms. Its core ring system (ABCD), composed of 17 carbon atoms, is ...
s responsible for the development and regulation of the female
reproductive system The reproductive system of an organism, also known as the genital system, is the biological system made up of all the anatomical organs An organ is a group of tissues with similar functions. Plant life and animal life rely on many organs tha ...
and
secondary sex characteristic Secondary sex characteristics are features that appear during puberty Puberty is the process of physical changes through which a child Biologically, a child (plural children) is a human Humans (''Homo sapiens'') are the most ab ...
s. There are three major
endogenous Endogenous substances and processes are those that originate from within a system such as an organism In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Bi ...
estrogens that have estrogenic hormonal activity:
estrone Estrone (E1), also spelled oestrone, is a steroid A steroid is a biologically active organic compound In chemistry Chemistry is the study of the properties and behavior of . It is a that covers the that make up matter to the ...

estrone
(E1),
estradiol Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous cycle, estrous and menstrual cycle, menstrual female reproductive cycles. Estradiol is resp ...

estradiol
(E2), and
estriol Estriol (E3), also spelled oestriol, is a steroid A steroid is a biologically active organic compound In chemistry Chemistry is the study of the properties and behavior of . It is a that covers the that make up matter to the ...

estriol
(E3). Estradiol, an
estrane Estrane is a C18 steroid derivative, with a gonane core. ''Estrenes'' are estrane derivatives that contain a double bond, with an example being nandrolone. ''Estratrienes'' (estrins) are estrane derivatives that contain three double bonds, for i ...

estrane
, is the most potent and prevalent. Another estrogen called
estetrol Estetrol (E4), or oestetrol, is a weak estrogen Estrogens or oestrogens, are a class of natural or synthetic s responsible for the development and regulation of the female and s. There are three major estrogens that have estrogenic hormon ...

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
androgen An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone A steroid hormone is a steroid , hypothetical a steroid with 32 carbon atoms. Its core ring system (ABCD), composed of 17 c ...
s 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 hormone A steroid hormone is a steroid A steroid is a biologically active organic compound In , organic compounds are generally any s that contain - . Due to carbon's ability to (form chains with other carbon s), millions of organic compounds ...
s, estrogens readily
diffuse 250px, Diffusion from a microscopic and macroscopic point of view. Initially, there are solution, solute molecules on the left side of a barrier (purple line) and none on the right. The barrier is removed, and the solute diffuses to fill the wh ...

diffuse
across the
cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane A biological membrane, biomembrane or cell membrane is a selectively permeable membra ...

cell membrane
. Once inside the cell, they bind to and activate
estrogen receptor Estrogen receptors (ERs) are a group of proteins found inside cell (biology), cells. They are receptor (biochemistry), receptors that are activated by the hormone estrogen (17β-estradiol). Two classes of ER exist: nuclear estrogen receptors (ER ...
s (ERs) which in turn the of many
gene In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mecha ...

gene
s. Additionally, estrogens bind to and activate rapid-signaling
membrane estrogen receptorMembrane estrogen receptors (mERs) are a group of receptors which bind estrogen Estrogen, or oestrogen, is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteri ...
s (mERs), such as
GPER G protein-coupled estrogen receptor 1 (GPER), also known as G protein-coupled receptor 30 (GPR30), is a protein that in humans is encoded by the ''GPER'' gene. GPER binds to and is activated by the female sex hormone estradiol and is responsible f ...
(GPR30). In addition to their role as natural hormones, estrogens are used as
medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, therapy, treat, or preventive medicine, prevent disease. Drug therapy (pharmacotherapy) ...

medication
s, for instance in
menopausal hormone therapy Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat menopausal symptoms, symptoms associated with female menopause. These symptoms can include ho ...
,
hormonal birth control Hormonal contraception refers to birth control Birth control, also known as contraception, anticonception, and fertility control, is a method or device used to prevent pregnancy Pregnancy, also known as gestation, is the time during w ...
and
feminizing hormone therapy Feminizing hormone therapy, also known as transfeminine hormone therapy, is hormone therapy Hormone therapy or hormonal therapy is the use of hormones A hormone (from the Greek Greek may refer to: Greece Anything of, from, or related to Gr ...
for
transgender women A trans woman is a woman A woman is an adult female Female (symbol: ♀) is the sex of an organism that produces the large non-mobile ovum, ova (egg cells), the type of gamete (sex cell) that fuses with the Sperm, male gamete during ...
and nonbinary people.


Types and examples

The four major naturally occurring estrogens in women are
estrone Estrone (E1), also spelled oestrone, is a steroid A steroid is a biologically active organic compound In chemistry Chemistry is the study of the properties and behavior of . It is a that covers the that make up matter to the ...

estrone
(E1),
estradiol Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous cycle, estrous and menstrual cycle, menstrual female reproductive cycles. Estradiol is resp ...

estradiol
(E2),
estriol Estriol (E3), also spelled oestriol, is a steroid A steroid is a biologically active organic compound In chemistry Chemistry is the study of the properties and behavior of . It is a that covers the that make up matter to the ...

estriol
(E3), and
estetrol Estetrol (E4), or oestetrol, is a weak estrogen Estrogens or oestrogens, are a class of natural or synthetic s responsible for the development and regulation of the female and s. There are three major estrogens that have estrogenic hormon ...

estetrol
(E4). Estradiol is the predominant estrogen during reproductive years both in terms of absolute serum levels as well as in terms of estrogenic activity. During
menopause 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 48 and 52. Medical professionals often ...
, estrone is the predominant circulating estrogen and during pregnancy estriol is the predominant circulating estrogen in terms of serum levels. Given by
subcutaneous injection A subcutaneous injection is administered as a bolus into the subcutis The subcutaneous tissue (), also called the hypodermis, hypoderm (), subcutis, superficial fascia, is the lowermost layer of the integumentary system The integumentary ...

subcutaneous injection
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 Menstruation, 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 fe ...
and menopause stages of life. However, during
pregnancy Pregnancy, also known as gestation, is the time during which one or more offspring In biology, offspring are the young creation of living organisms, produced either by a Asexual reproduction, single organism or, in the case of sexual repr ...

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 Estetrol (E4), or oestetrol, is a weak estrogen Estrogens or oestrogens, are a class of natural or synthetic s responsible for the development and regulation of the female and s. There are three major estrogens that have estrogenic hormon ...

estetrol
(E4) is produced only during pregnancy. All of the different forms of estrogen are synthesized from
androgen An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone A steroid hormone is a steroid , hypothetical a steroid with 32 carbon atoms. Its core ring system (ABCD), composed of 17 c ...
s, specifically
testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testes and prostate, as well as promoting secondar ...
and
androstenedione Androstenedione, or 4-androstenedione (abbreviated as A4 or Δ4-dione), also known as androst-4-ene-3,17-dione, is an endogenous Endogenous substances and processes are those that originate from within a system such as an organism, Tissue (bio ...

androstenedione
, by the
enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates in ...

enzyme
aromatase Aromatase, also called estrogen synthetase or estrogen synthase, is an enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are cal ...
. Minor endogenous estrogens, the biosyntheses of which do not involve
aromatase Aromatase, also called estrogen synthetase or estrogen synthase, is an enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are cal ...
, include
27-hydroxycholesterol 27-Hydroxycholesterol (27-HC) is an endogenous oxysterol with multiple biological functions, including activity as a selective estrogen receptor modulator (SERM) (a mixed, tissue-specific agonist-antagonist of the estrogen receptor (ER)) and as an ...

27-hydroxycholesterol
,
dehydroepiandrosterone Dehydroepiandrosterone (DHEA), also known as androstenolone, is an endogenous Endogenous substances and processes are those that originate from within a system such as an organism, Tissue (biology), tissue, or Cell (biology), cell. Endogenous ...

dehydroepiandrosterone
(DHEA),
7-oxo-DHEA 7-Ketodehydroepiandrosterone (7-keto-DHEA,7-oxo-DHEA), also known as 7-oxoprasterone, is a prohormone A hormone (from the Greek participle , "setting in motion") is any member of a class of signaling molecules in multicellular organisms, that ...
, 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 Endogenous substances and processes are those that originate from within a system such as an organism, Tissue (bio ...

androstenedione
(A4),
androstenediol Androstenediol, or 5-androstenediol (abbreviated as A5 or Δ5-diol), also known as androst-5-ene-3β,17β-diol, is an endogenous weak androgen An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic ...
(A5), 3α-androstanediol, and 3β-androstanediol. Some estrogen metabolites, such as the
catechol estrogen A catechol estrogen is a steroid , a steroid with 27 carbon atoms. Its core ring system (ABCD), composed of 17 carbon atoms, is shown with IUPAC The International Union of Pure and Applied Chemistry (IUPAC ) is an international federation o ...
s
2-hydroxyestradiol 2-Hydroxyestradiol (2-OHE2), also known as estra-1,3,5(10)-triene-2,3,17β-triol, is an endogenous Endogenous substances and processes are those that originate from within a system such as an organism, Tissue (biology), tissue, or Cell (biology), c ...

2-hydroxyestradiol
,
2-hydroxyestrone 2-Hydroxyestrone (2-OHE1), also known as estra-1,3,5(10)-trien-2,3-diol-17-one, is an endogenous, natural product, naturally occurring catechol estrogen and a major metabolite of estrone and estradiol. It is formed irreversible reaction, irreversib ...

2-hydroxyestrone
,
4-hydroxyestradiol 4-Hydroxyestradiol (4-OHE2), also known as estra-1,3,5(10)-triene-3,4,17β-triol, is an endogenous, natural product, naturally occurring catechol estrogen and a minor metabolite of estradiol. It is estrogenic, similarly to many other hydroxylated e ...

4-hydroxyestradiol
, and
4-hydroxyestrone 4-Hydroxyestrone (4-OHE1), also known as estra-1,3,5(10)-triene-3,4-diol-17-one, is an endogenous, naturally occurring catechol estrogen and a minor metabolite of estrone and estradiol Estradiol (E2), also spelled oestradiol, is an estrogen ...

4-hydroxyestrone
, as well as
16α-hydroxyestrone 16α-Hydroxyestrone (16α-OH-E1), or hydroxyestrone, also known as estra-1,3,5(10)-triene-3,16α-diol-17-one, is an endogenous Endogenous substances and processes are those that originate from within a system such as an organism, Tissue (biology), ...

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 Estrogen receptors (ERs) are a group of proteins found inside cell (biology), cells. They are receptor (biochemistry), receptors that are activated by the hormone estrogen (17β-estradiol). Two classes of ER exist: nuclear estrogen receptors (ER ...
(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 ...

gene expression
. 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 A hormone response element (HRE) is a short sequence of DNA Deoxyribonucleic acid (; DNA) is a molecule A scanning tunneling microscopy image of pentacene molecules, which consist of linear chains of five carbon rings. A molecule i ...
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 A man is an adult male Male (symbol: ♂) is the sex of an organism that produces the gamete (sex cell) known as sperm, which fuses with the larger female gamete, or ovum, in the process of fertilization. A male organism cannot sexual r ...

men
and
women A woman is an adult female Female (symbol: ♀) is the sex of an organism that produces the large non-mobile ovum, ova (egg cells), the type of gamete (sex cell) that fuses with the Sperm, male gamete during sexual reproduction. A female ...

women
, they are usually present at significantly higher levels in women of reproductive age. They promote the development of female
secondary sexual characteristic Secondary sex characteristics are features that appear during puberty Puberty is the process of physical changes through which a child Biologically, a child (plural children) is a human Humans (''Homo sapiens'') are the most ab ...
s, such as
breasts The breast is one of two prominences located on the upper ventral region of the torso of primates. In females, it serves as the mammary gland, which produces and secretes milk to feed infants. Both females and males develop breasts from the ...

breasts
, and are also involved in the thickening of the
endometrium The endometrium is the inner epithelial Epithelium is one of the four basic types of animal Tissue (biology), tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly pac ...

endometrium
and other aspects of regulating the menstrual cycle. In males, estrogen regulates certain functions of the
reproductive system The reproductive system of an organism, also known as the genital system, is the biological system made up of all the anatomical organs An organ is a group of tissues with similar functions. Plant life and animal life rely on many organs tha ...
important to the maturation of
sperm Sperm is the male reproductive Cell (biology), 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 ...

sperm
and may be necessary for a healthy
libido Libido (; colloquial Colloquialism or colloquial language is the style (sociolinguistics), linguistic style used for casual (informal) communication. It is the most common functional style of speech, the idiom normally employed in conversation ...
.


Overview of actions

* Structural **
Anabolic Anabolism () is the set of metabolic pathway In biochemistry, a metabolic pathway is a linked series of chemical reaction A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation ...
: Increases
muscle mass Skeletal muscles (commonly referred to as muscles) are organs An organ is a group of tissues with similar functions. Plant life and animal life rely on many organs that co-exist in organ systems. A given organ's tissues can be broadly cate ...
and strength, speed of muscle regeneration, and
bone density Bone density, or bone mineral density (BMD), is the amount of bone mineral Bone mineral (also called inorganic bone phase, bone salt, or bone apatite) is the inorganic In chemistry Chemistry is the scientific discipline involved with Chemic ...

bone density
, increased sensitivity to exercise, protection against muscle damage, stronger
collagen Collagen () is the main structural protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and Sir John Cowder ...

collagen
synthesis, increases the collagen content of connective tissues,
tendon A tendon or sinew is a tough, high-tensile-strength band of dense fibrous connective tissue that connects muscle Skeletal muscles (commonly referred to as muscles) are organs An organ is a group of tissues with similar functions. Plant ...

tendon
s, and
ligament A ligament is the Connective tissue#Types, 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 incl ...

ligament
s, but also decreases stiffness of
tendon A tendon or sinew is a tough, high-tensile-strength band of dense fibrous connective tissue that connects muscle Skeletal muscles (commonly referred to as muscles) are organs An organ is a group of tissues with similar functions. Plant ...

tendon
s and
ligament A ligament is the Connective tissue#Types, 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 incl ...

ligament
s (especially during
menstruation Menstruation (also known as a period and many other Colloquialism, colloquial terms) is the regular discharge of blood and Mucous membrane, mucosal tissue from the endometrium, inner lining of the uterus through the vagina. The menstrual cycl ...
). 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 Secondary sex characteristics are features that appear during puberty in humans, and at sexual maturity in other animals. These characteristics are particularly evident in the sexual dimorphism, sexually dimorphic phenotypic traits that distinguis ...
** Accelerate
metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life Life is a characteristic that distinguishes physical entities A bubble of exhaled gas in water In common usage and classical mechanics, a phys ...

metabolism
** Increased fat storage in some body parts such as breasts, buttocks, and legs but decreased abdominal and
visceral fat Adipose tissue, body fat, or simply fat is a loose connective tissue Connective tissue is one of the many basic types of animal Animals (also called Metazoa) are multicellular eukaryotic organisms that form the Kingdom (biology), biolo ...
(androgenic obesity).
Estradiol Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous cycle, estrous and menstrual cycle, menstrual female reproductive cycles. Estradiol is resp ...

Estradiol
also regulates energy expenditure, body weight
homeostasis In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mechanis ...
, 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 growth ** Increase
uterine The uterus (from Latin "uterus", plural ''uteri'') or womb () is a major female hormone-responsive sex organ, secondary sex organ of the reproductive system in humans and most other mammals. Things occurring in the uterus are described with the ...

uterine
growth ** Increase
vaginal lubrication Vaginal lubrication is a naturally produced fluid that lubricates a vagina In mammal Mammals (from Latin language, Latin , 'breast') are a group of vertebrate animals constituting the class (biology), class Mammalia (), and charact ...

vaginal lubrication
** Thicken the
vagina In mammal Mammals (from Latin language, Latin , 'breast') are a group of vertebrate animals constituting the class (biology), class Mammalia (), and characterized by the presence of mammary glands which in Female#Mammalian female, femal ...

vagina
l wall ** Maintenance of vessel and skin ** Reduce
bone resorption Bone resorption is resorption Resorption is the absorption into the circulatory system of cells or tissue, usually by osteoclast, osteoclasts. Types of resorption include: * Bone resorption * Herniated Disc Resorption * Tooth resorption * Fetal r ...
, increase bone formation *
Protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and Sir John Cowdery Kendrew in 1958, for which they received a No ...

Protein
synthesis ** Increase hepatic production of
binding proteinA binding protein is any protein that acts as an agent to Molecular binding, bind two or more molecules together. Examples include: *DNA-binding protein **Single-strand binding protein **Telomere-binding protein *RNA-binding protein **Poly(A)-bindi ...
s *
Coagulation Coagulation, also known as clotting, is the process by which blood Blood is a body fluid Body fluids, bodily fluids, or biofluids are liquid A liquid is a nearly incompressible In fluid mechanics or more generally continuum mech ...
** Increase circulating level of factors 2, 7, , ,
plasminogen Plasmin is an important enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enz ...
** Decrease
antithrombin Antithrombin (AT) is a small protein molecule that inactivates several enzymes of the coagulation Coagulation, also known as clotting, is the process by which blood Blood is a body fluid Body fluids, bodily fluids, or biofluids are liq ...

antithrombin
III ** Increase
platelet Platelets, also called thrombocytes (from Greek#REDIRECT Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic Republic, is a country located in Southeast Europe. ...

platelet
adhesiveness ** Increase vWF (estrogen ->
Angiotensin II Angiotensin is a peptide hormonePeptide hormones or protein hormones are hormones whose molecules are peptides or proteins, respectively. The latter have longer amino acid chain lengths than the former. These hormones have an effect on the endocr ...
->
Vasopressin Vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone A hormone (from the Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ...

Vasopressin
) ** Increase
PAI-1 Plasminogen activator inhibitor-1 (PAI-1) also known as endothelial plasminogen activator inhibitor or serpin E1 is a protein that in humans is encoded by the ''SERPINE1'' gene. Elevated PAI-1 is a risk factor for thrombosis and atherosclerosis P ...
and PAI-2 also through Angiotensin II *
Lipid In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mechanis ...
** Increase HDL,
triglyceride A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester An ester is a derived from an (organic or inorganic) in which at least one –OH group is replaced by an –O– () group, as in the substitution reaction of a an ...

triglyceride
** Decrease
LDL Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein 250px, Structure of a chylomicron. ApoA, ApoB, ApoC, ApoE are apolipoproteins; green particles are phospholipids; T is triacylglycerol; C is cholesterol ester. A lipo ...
, fat deposition * Fluid balance ** Salt (
sodium Sodium is a chemical element In chemistry, an element is a pure Chemical substance, substance consisting only of atoms that all have the same numbers of protons in their atomic nucleus, nuclei. Unlike chemical compounds, chemical eleme ...
) 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. ...

cortisol
,
SHBG Sex hormone-binding globulin (SHBG) or sex steroid-binding globulin (SSBG) is a glycoprotein Glycoproteins are protein Proteins are large s and s that comprise one or more long chains of . Proteins perform a vast array of functions wit ...
*
Gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system The human digestive system consists of the gastrointestinal tract The gastrointestinal tract, (GI tract, GIT, d ...
** Reduce bowel motility ** Increase
cholesterol Cholesterol is any of a class of certain organic compound, organic molecules. A cholesterol is a sterol (or chemical modification, modified steroid), a type of lipid. Cholesterol is biosynthesis, biosynthesized by all animal Cell (biology)#Euk ...

cholesterol
in
bile Bile (from latin ''bilis''), or gall, is a dark-green-to-yellowish-brown fluid produced by the liver The liver is an organ Organ may refer to: Biology * Organ (anatomy) An organ is a group of Tissue (biology), tissues with similar fun ...
*
Melanin Melanin (; from el, μέλας ''melas'', "black, dark") is a broad term for a group of natural pigments found in most organisms. Melanin is produced through a multistage chemical process known as melanogenesis, where the oxidation of the ami ...

Melanin
** Increase
pheomelanin Melanin (; from el, μέλας ''melas'', "black, dark") is a broad term for a group of natural pigment A pigment is a colored material that is completely or nearly insoluble in water. In contrast, dyes are typically soluble, at least at ...
, reduce
eumelanin Melanin (; from el, μέλας ''melas'', "black, dark") is a broad term for a group of natural pigment A pigment is a colored material that is completely or nearly insoluble in water. In contrast, dyes are typically soluble, at least at ...
* Cancer ** Support hormone-sensitive breast cancers (see section below) *
Lung function The lungs are the primary organs An organ is a group of tissues with similar functions. Plant life and animal life rely on many organs that co-exist in organ systems. A given organ's tissues can be broadly categorized as parenchyma ...
** Promotes lung function by supporting
alveoli Alveolus (pl. alveoli, adj. alveolar) is a general anatomical term for a concave cavity or pit. Alveolus may refer to: In anatomy and zoology in general * Pulmonary alveolus, an air sac in the lungs ** Alveolar cell or pneumocyte ** Alveolar duct ...
(in rodents but probably in humans). *
Uterus The uterus (from Latin "uterus", plural ''uteri'') or womb () is the main female hormone-responsive, sex organ, secondary sex organ of the reproductive system in humans and most other mammals. Things occurring in the uterus are described with t ...

Uterus
lining ** Estrogen together with
progesterone Progesterone (P4) is an endogenous Endogenous substances and processes are those that originate from within a system such as an organism, Tissue (biology), tissue, or Cell (biology), cell. Endogenous substances and processes contrast with exo ...

progesterone
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 hormonePeptide hormones or protein hormones are hormones whose molecules are peptides or proteins, respectively. The latter have longer amino acid chain lengths than the former. These hormones have an effect o ...

oxytocin
receptor in myometrium *
Ovulation Ovulation is the release of egg An egg is the organic vessel containing the in which an develops until it can survive on its own, at which point the animal hatches. An egg results from of an . Most s, (excluding s), and lay eggs, alth ...

Ovulation
** Surge in estrogen level induces the release of
luteinizing hormone Luteinizing hormone (LH, also known as lutropin and sometimes lutrophin) is a hormone A hormone (from the Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic R ...
, which then triggers ovulation by releasing the egg from the
Graafian follicle An ovarian follicle is a roughly spheroid cellular aggregation set found in the ovaries The ovary is an organ found in the female reproductive system 400px, 1. Labia_majora.html"_;"title="Vulva: 2. Labia_majora">Vulva: 2. Labia ...

Graafian follicle
in the
ovary The ovary is an organ found in the female reproductive system The female reproductive system is made up of the internal and external sex organs that function in reproduction of new offspring. In humans, the female reproductive system is im ...

ovary
. *
Sexual behavior Human sexual activity, human sexual practice or human sexual behaviour is the manner in which humans experience and express their Human sexuality, sexuality. People engage in a variety of sexual acts, ranging from activities done alone (e.g., ...
** Estrogen is required for female mammals to engage in
lordosis behavior Lordosis behavior, also known as mammalian lordosis (Greek lordōsis, from ''lordos'' "bent backward") or presenting, is the naturally occurring body posture for sexual receptivity to copulation present in most mammals including rodents R ...
during
estrus The estrous cycle (, originally ) is the set of recurring physiological changes that are induced by reproductive hormone A hormone (from the Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλ ...
(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 The hypothalamus (from Ancient Greek wikt:ὑπό, ὑπό, "under", and wikt:θάλαμος, θάλαμος, "chamber") is a portion of the brain that contains a number of small Nucleus (neuroanatomy), nuclei with a variety of functions. One of ...

hypothalamus
. **
Sex drive Libido (; colloquial: sex drive) is a person's overall sexual drive or desire for sexual activity. In psychoanalytic theory libido is psychic drive or energy, particularly associated with sexual instinct, but also present in other instinctive ...

Sex drive
is dependent on
androgen An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone A steroid hormone is a steroid , hypothetical a steroid with 32 carbon atoms. Its core ring system (ABCD), composed of 17 c ...
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 #REDIRECT Hypoactive sexual desire disorder Hypoactive sexual desire disorder (HSDD), hyposexuality or inhibited sexual desire (ISD) is considered a sexual dysfunction and is characterized as a lack or absence of sexual fantasies and desire for s ...
, 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 characteristic Secondary sex characteristics are features that appear during puberty Puberty is the process of physical changes through which a child Biologically, a child (plural children) is a human Humans (''Homo sapiens'') are the most ab ...
s during
puberty Puberty is the process of physical changes through which a child Biologically, a child (plural children) is a human Humans (''Homo sapiens'') are the most abundant and widespread species In biology Biology is the natur ...

puberty
, including
breast development Breast development, also known as mammogenesis, is a complex biological process Biological processes are those processes that are vital for an organism In biology, an organism () is any organic, life, living system that functions as ...
, widening of the
hip In vertebrate Vertebrates () comprise all species of animal Animals (also called Metazoa) are multicellular eukaryotic organisms that form the Kingdom (biology), biological kingdom Animalia. With few exceptions, animals Heterotroph, ...

hip
s, and female
fat distribution Human body shape is a complex phenomenon with sophisticated detail and function. The general shape or figure of a person is defined mainly by the molding of skeletal structures, as well as the distribution of muscle Skeletal muscles (commonl ...
. Conversely,
androgen An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone A steroid hormone is a steroid , hypothetical a steroid with 32 carbon atoms. Its core ring system (ABCD), composed of 17 c ...
s are responsible for 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 androgenic ...
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 Acne, also known as acne vulgaris, is a long-term skin condition A skin condition, also known as cutaneous condition, is any medical condition A disease is a particular abnormal condition that negatively affects the structure or ...
and axillary odor.


Breast development

Estrogen, in conjunction with
growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell (biology), cell reproduction, and cell regeneration in humans and other animals. It is th ...
(GH) and its secretory product
insulin-like growth factor 1 Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a hormone similar in tertiary structure, molecular structure to insulin which plays an important role in childhood growth, and has Anabolism, anabolic effects in adults. IGF-1 is ...
(IGF-1), is critical in mediating breast development during
puberty Puberty is the process of physical changes through which a child Biologically, a child (plural children) is a human Humans (''Homo sapiens'') are the most abundant and widespread species In biology Biology is the natur ...

puberty
, as well as breast maturation during
pregnancy Pregnancy, also known as gestation, is the time during which one or more offspring In biology, offspring are the young creation of living organisms, produced either by a Asexual reproduction, single organism or, in the case of sexual repr ...

pregnancy
in preparation of
lactation Lactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process naturally occurs with all post-pregnancy female mammals, although it may predate mammals. The process ...

lactation
and
breastfeeding Breastfeeding, also called nursing, is the process of feeding a mother's breast milk to her infant, either directly from the breast or by expressing (pumping out) the milk from the breast and bottle-feeding it to the infant. The World Healt ...

breastfeeding
. Estrogen is primarily and directly responsible for inducing the ductal component of breast development, as well as for causing fat deposition and
connective tissue Connective tissue is one of the many basic types of animal Animals (also called Metazoa) are multicellular A multicellular organism is an organism In biology, an organism () is any organic, life, living system that functions ...
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 In the field of molecular biology, nuclear receptors are a class of proteins found within cells that are responsible for sensing Steroid hormone, steroid and Thyroid hormo ...
expression in the breasts and by inducing the secretion of
prolactin Prolactin, also known as lactotropin, is a protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and Sir Jo ...
. Allowed for by estrogen,
progesterone Progesterone (P4) is an endogenous Endogenous substances and processes are those that originate from within a system such as an organism, Tissue (biology), tissue, or Cell (biology), cell. Endogenous substances and processes contrast with exo ...

progesterone
and prolactin work together to complete lobuloalveolar development during pregnancy.
Androgen An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone A steroid hormone is a steroid , hypothetical a steroid with 32 carbon atoms. Its core ring system (ABCD), composed of 17 c ...
s such as testosterone powerfully oppose estrogen action in the breasts, such as by reducing
estrogen receptor Estrogen receptors (ERs) are a group of proteins found inside cell (biology), cells. They are receptor (biochemistry), receptors that are activated by the hormone estrogen (17β-estradiol). Two classes of ER exist: nuclear estrogen receptors (ER ...
expression in them.


Female reproductive system

Estrogens are responsible for maturation and maintenance of the
vagina In mammal Mammals (from Latin language, Latin , 'breast') are a group of vertebrate animals constituting the class (biology), class Mammalia (), and characterized by the presence of mammary glands which in Female#Mammalian female, femal ...

vagina
and
uterus The uterus (from Latin "uterus", plural ''uteri'') or womb () is the main female hormone-responsive, sex organ, secondary sex organ of the reproductive system in humans and most other mammals. Things occurring in the uterus are described with t ...

uterus
, and are also involved in
ovarian The ovary is an organ found in the female reproductive system The female reproductive system is made up of the internal and external sex organs that function in reproduction of new offspring. In humans, the female reproductive system is im ...

ovarian
function, such as maturation of
ovarian follicle An ovarian follicle is a roughly spheroid cellular aggregation set found in the ovaries The ovary is an organ found in the female reproductive system 400px, 1. Labia_majora.html"_;"title="Vulva: 2. Labia_majora">Vulva: 2. Labia ...

ovarian follicle
s. In addition, estrogens play an important role in regulation of
gonadotropin Gonadotropins are glycoprotein Glycoproteins are protein Proteins are large s and s that comprise one or more long chains of . Proteins perform a vast array of functions within organisms, including , , , providing and , and from one ...
secretion Secretion is the movement of material from one point to another, such as a secreted chemical substance A chemical substance is a form of matter In classical physics and general chemistry, matter is any substance that has mass and takes up ...
. For these reasons, estrogens are required for female
fertility Fertility is the capability to produce offspring through reproduction following the onset of sexual maturity. The fertility rate is the average number of children born by a female during her lifetime and is quantified Demography, demographicall ...
.


Neuroprotection and DNA repair

Estrogen regulated
DNA repair DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA Deoxyribonucleic acid (; DNA) is a molecule File:Pentacene on Ni(111) STM.jpg, A scanning tunneling microscopy image of pentacene mol ...

DNA repair
mechanisms in the
brain A brain is an organ Organ may refer to: Biology * Organ (anatomy) An organ is a group of Tissue (biology), tissues with similar functions. Plant life and animal life rely on many organs that co-exist in organ systems. A given organ's tis ...

brain
have neuroprotective effects. Estrogen regulates the transcription of DNA
base excision repair Base excision repair (BER) is a cellular mechanism, studied in the fields of biochemistry Biochemistry or biological chemistry, is the study of es within and relating to living s. A sub-discipline of both and , biochemistry may be divided ...
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 Libido (; colloquial Colloquialism or colloquial language is the style (sociolinguistics), linguistic style used for casual (informal) communication. It is the most common functional style of speech, the idiom normally employed in conversation ...
(sex drive) in both women and men.


Cognition

Verbal memory Verbal memory is a term used in cognitive psychology Cognitive psychology is the scientific study of mental process Cognition () refers to "the mental action or process of acquiring knowledge and understanding through thought, experience, a ...
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 many aspects of intellectual function Intellectual functioning refers to the "general men ...
. 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 In mammalian brain A brain is an organ that serves as the center of the nervous system In Biology, biology, the nervous system is a Complex system, highly complex part of an animal that coordinates its Behavior, actions and Sense, senso ...

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 Mental health is "a state of well-being Well-being, also known as ''wellness'', ''prudential value'' or ''quality of life'', refers to what is intrinsically valuable relative ''to'' someone. So the well-being of a person is what is ultimatel ...

mental health
. Sudden estrogen withdrawal, fluctuating estrogen, and periods of sustained low estrogen levels correlate with significant mood lowering. Clinical recovery from
postpartum The postpartum (or postnatal) period begins immediately after childbirth Childbirth, also known as labour or delivery, is the ending of pregnancy Pregnancy, also known as gestation, is the time during which one or more offspring In ...
,
perimenopause Menopause, also known as the climacteric, is the time in women's lives when menstrual periods The menstrual cycle is a series of natural changes in hormone A hormone (from the Greek Greek may refer to: Greece Anything of, from, or rel ...
, and
postmenopause Menopause, also known as the climacteric, is the time in women's lives when menstrual periods The menstrual cycle is a series of natural changes in hormone A hormone (from the Greek Greek may refer to: Greece Anything of, from, or rel ...
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 Premenstrual dysphoric disorder (PMDD) is a severe and disabling form of premenstrual syndrome affecting 1.8–5.8% of menstruating women. Code: 625.4 (N94.3) The disorder consists of a variety of affective, behavioral and somatic symptoms that re ...
. 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 Aromatase, also called estrogen synthetase or estrogen synthase, is an enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are cal ...
in male lab mice, OCD rituals were dramatically decreased.
Hypothalamic The hypothalamus (from Ancient Greek wikt:ὑπό, ὑπό, "under", and wikt:θάλαμος, θάλαμος, "chamber") is a portion of the brain that contains a number of small Nucleus (neuroanatomy), nuclei with a variety of functions. One of ...

Hypothalamic
protein levels in the gene
COMT Catechol-''O''-methyltransferase (COMT; ) is one of several enzymes that degrade catecholamines (such as dopamine, epinephrine, and norepinephrine), Catechol estrogen, catecholestrogens, and various drugs and substances having a catechol structu ...
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. Contrarily, local application of estrogen has been shown to block the ability of
fluvoxamine Fluvoxamine, sold under brand names such as Luvox, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is primarily used to treat major depressive disorder and obsessive–compulsive disorder (OCD), but is also u ...

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 Binge eating is a pattern of disordered eating Disordered eating describes a variety of abnormal eating behaviors that, by themselves, do not warrant diagnosis of an eating disorder An eating disorder is a mental disorder A mental disord ...
. 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 (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 A hormone (from the Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic Republic, is a country l ...

menstrual cycle
. Research has predicted increased emotional eating during hormonal flux, which is characterized by high
progesterone Progesterone (P4) is an endogenous Endogenous substances and processes are those that originate from within a system such as an organism, Tissue (biology), tissue, or Cell (biology), cell. Endogenous substances and processes contrast with exo ...

progesterone
and
estradiol Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous cycle, estrous and menstrual cycle, menstrual female reproductive cycles. Estradiol is resp ...

estradiol
levels that occur during the mid-
luteal phase The menstrual cycle The menstrual cycle is a series of natural changes in hormone A hormone (from the Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic Re ...
. 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, which limits
height Height is measure of vertical distance Distance is a numerical measurement ' Measurement is the number, numerical quantification (science), quantification of the variable and attribute (research), attributes of an object or event, which can ...
and
limb Limb can refer to: *Limb (anatomy), an appendage of a human or animal *Limb Music, a record label *Limb (album), an album by Foetus *Limb, in astronomy, the curved edge of the apparent disk of a celestial body, e.g. lunar limb *Limb, a large or mai ...
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 (BMD), is the amount of bone mineral Bone mineral (also called inorganic bone phase, bone salt, or bone apatite) is the inorganic In chemistry Chemistry is the scientific discipline involved with Chemic ...
throughout life. Due to hypoestrogenism, the risk of
osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone massImage:Bone density scanner.jpg, A scanner used to measure bone density using dual energy X-ray absorptiometry Bone density, or bone mineral density (BMD), is the amount ...
increases during
menopause 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 48 and 52. Medical professionals often ...
.


Cardiovascular system

Women suffer less from 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 Pregnancy, also known as gestation, is the time during which one or more offspring In biology, offspring are the young creation of living organisms, produced either by a Asexual reproduction, single organism or, in the case of sexual repr ...

pregnancy
, high levels of estrogens increase
coagulation Coagulation, also known as clotting, is the process by which blood Blood is a body fluid Body fluids, bodily fluids, or biofluids are liquid A liquid is a nearly incompressible In fluid mechanics or more generally continuum mech ...
and the risk of
venous thromboembolism Venous thrombosis is blockage of a vein Veins are blood vessels The blood vessels are the components of the circulatory system The circulatory system, also called the cardiovascular system or the vascular system, is an Biological syste ...
.


Immune system

Estrogen has
anti-inflammatory Anti-inflammatory (or antiinflammatory) is the property of a substance or treatment that reduces inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogen ...
properties and helps in mobilization of polymorphonuclear white blood cells or
neutrophil Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocyte Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. They are also called po ...

neutrophil
s.


Associated conditions

Researchers have implicated estrogens in various
estrogen-dependent condition An estrogen-dependent condition, disease, disorder, or syndrome, is a medical condition that is, in part or full, dependent on, or is sensitive to, the presence of estrogenic activity in the body. Known estrogen-dependent conditions include mastody ...
s, such as ER-positive
breast cancer Breast cancer is cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumor A benign tumor is a mass of cells Cell most o ...

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 In the fields of molecular biology Molecular biology is the branch of biology Biology is the natural science that studies life and li ...
s involving estrogen signaling or metabolism, such as
estrogen insensitivity syndrome Estrogen insensitivity syndrome (EIS), or estrogen resistance, is a form of congenital estrogen deficiency or hypoestrogenism which is caused by a defective estrogen receptor (ER) – specifically, the estrogen receptor alpha (ERα) – that resu ...
,
aromatase deficiency Aromatase deficiency is a very rare condition characterised by the extremely low or absence of the enzyme aromatase activity in the body. It is an autosomal recessive disease resulted from various mutations of gene CPY19 (P450arom) which can lead ...
, and
aromatase excess syndrome Aromatase excess syndrome (AES or AEXS) is a rare genetic disorder, genetic and endocrine disease, endocrine syndrome which is characterized by an gene expression, overexpression of aromatase, the enzyme responsible for the biosynthesis of the estr ...
. High estrogen can amplify stress-hormone responses in stressful situations.


Biochemistry


Biosynthesis

Estrogens, in females, are produced primarily by the
ovaries The ovary is an organ found in the female reproductive system 300px, 1. Labia_majora.html"_;"title="Vulva: 2. Labia_majora">Vulva: 2. Labia_majora; 3. Labia_minora; 4. Vulval_vestibule.html" "title="Labia_minora.html ...

ovaries
, and during pregnancy, the
placenta The placenta is a temporary fetal organ Organ may refer to: Biology * Organ (anatomy) An organ is a group of Tissue (biology), tissues with similar functions. Plant life and animal life rely on many organs that co-exist in organ systems. ...

placenta
.
Follicle-stimulating hormone Follicle-stimulating hormone (FSH) is a gonadotropin Gonadotropins are glycoprotein hormones secreted by gonadotropic cells of the anterior pituitary A major Organ (anatomy), organ of the endocrine system, the anterior pituitary (also call ...
(FSH) stimulates the ovarian production of estrogens by the
granulosa cell A granulosa cell or follicular cell is a somatic cell A somatic cell (from Ancient Greek Ancient Greek includes the forms of the Greek language Greek ( el, label=Modern Greek Modern Greek (, , or , ''Kiní Neoellinikí Glóssa'' ...
s of the
ovarian follicle An ovarian follicle is a roughly spheroid cellular aggregation set found in the ovaries The ovary is an organ found in the female reproductive system 400px, 1. Labia_majora.html"_;"title="Vulva: 2. Labia_majora">Vulva: 2. Labia ...

ovarian follicle
s and
corpora lutea The ''corpus luteum'' (Latin for "yellow body"; plural ''corpora lutea'') is a temporary endocrine structure in female ovaries and is involved in the production of relatively high levels of progesterone and moderate levels of estradiol and inhibin ...
. Some estrogens are also produced in smaller amounts by other tissues such as the
liver The liver is an organ Organ may refer to: Biology * Organ (anatomy) An organ is a group of Tissue (biology), tissues with similar functions. Plant life and animal life rely on many organs that co-exist in organ systems. A given organ's t ...

liver
,
pancreas The pancreas is an Organ (anatomy), organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdominal cavity, abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine ...

pancreas
,
bone A bone is a rigid tissue Tissue may refer to: Biology * Tissue (biology), an ensemble of similar cells that together carry out a specific function * ''Triphosa haesitata'', a species of geometer moth found in North America * ''Triphosa dubit ...

bone
,
adrenal gland The adrenal glands (also known as suprarenal glands) are endocrine gland Endocrine glands are ductless glands of the endocrine system The endocrine system is a messenger system comprising feedback loops of the hormones released by interna ...

adrenal gland
s,
skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other cuticle, animal coverings, such as the arthropod exoskeleton, have differ ...

skin
,
brain A brain is an organ Organ may refer to: Biology * Organ (anatomy) An organ is a group of Tissue (biology), tissues with similar functions. Plant life and animal life rely on many organs that co-exist in organ systems. A given organ's tis ...

brain
,
adipose tissue Adipose tissue, body fat, or simply fat is a loose connective tissue Connective tissue is one of the many basic types of animal Animals (also called Metazoa) are multicellular eukaryotic organisms that form the Kingdom (biology), biolo ...

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 Endogenous substances and processes are those that originate from within a system such as an organism, Tissue (bio ...

androstenedione
from
cholesterol Cholesterol is any of a class of certain organic compound, organic molecules. A cholesterol is a sterol (or chemical modification, modified steroid), a type of lipid. Cholesterol is biosynthesis, biosynthesized by all animal Cell (biology)#Euk ...

cholesterol
. Androstenedione is a substance of weak androgenic activity which serves predominantly as a precursor (biochemistry), 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 (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 and 17,20-lyase, 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 A hormone (from the Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic Republic, is a country l ...

menstrual cycle
, 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 binding, plasma protein bound to human serum albumin, albumin and/or sex hormone-binding globulin in the circulation.


Metabolism

Estrogens are metabolism, metabolized via hydroxylation by cytochrome P450
enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates in ...

enzyme
s such as CYP1A1 and CYP3A4 and via conjugation (biochemistry), conjugation by estrogen sulfotransferases (sulfation) and UDP-glucuronyltransferases (glucuronidation). In addition, estradiol is dehydrogenation, dehydrogenated by 17β-hydroxysteroid dehydrogenase into the much less potent estrogen estrone. These reactions occur primarily in the
liver The liver is an organ Organ may refer to: Biology * Organ (anatomy) An organ is a group of Tissue (biology), tissues with similar functions. Plant life and animal life rely on many organs that co-exist in organ systems. A given organ's t ...

liver
, but also in other tissue (biology), tissues.


Excretion

Estrogens are excretion, excreted primarily by the kidneys as conjugation (biochemistry), conjugates via the urine.


Medical use

Estrogens are used as
medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, therapy, treat, or preventive medicine, prevent disease. Drug therapy (pharmacotherapy) ...

medication
s, mainly in hormonal contraception, hormone replacement therapy, and to treat gender dysphoria in
transgender women A trans woman is a woman A woman is an adult female Female (symbol: ♀) is the sex of an organism that produces the large non-mobile ovum, ova (egg cells), the type of gamete (sex cell) that fuses with the Sperm, male gamete during ...
and other Non-binary gender, transfeminine individuals as part of feminizing hormone therapy.


Chemistry

The estrogen steroid hormones are
estrane Estrane is a C18 steroid derivative, with a gonane core. ''Estrenes'' are estrane derivatives that contain a double bond, with an example being nandrolone. ''Estratrienes'' (estrins) are estrane derivatives that contain three double bonds, for i ...

estrane
steroids.


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 language, Greek (), literally meaning "verve or inspiration" but figuratively sexual passion or desire, and the suffix ''wikt:-gen, -gen'', meaning "producer of".


Environment

A range of synthetic and natural substances that possess estrogenic activity have been identified in the natural environment, environment and are referred to xenoestrogens. * Synthetic substances such as bisphenol A as well as metalloestrogens (e.g., cadmium). * Plant products with estrogenic activity are called phytoestrogens (e.g., coumestrol, daidzein, genistein, miroestrol). * Those produced by fungi are known as mycoestrogens (e.g., zearalenone). Estrogens are among the wide range of endocrine disruptor, 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. 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 drug, 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 Estrogens, 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