Estrogen receptor beta (ERβ) also known as NR3A2 (nuclear receptor subfamily 3, group A, member 2) is one of two main types of
estrogen receptor
Estrogen receptors (ERs) are proteins found in cell (biology), cells that function as receptor (biochemistry), receptors for the hormone estrogen (17β-estradiol). There are two main classes of ERs. The first includes the intracellular estrogen ...
—a
nuclear receptor
In the field of molecular biology, nuclear receptors are a class of proteins responsible for sensing steroids, thyroid hormones, vitamins, and certain other molecules. These intracellular receptors work with other proteins to regulate the ex ...
which is activated by the sex hormone
estrogen
Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...
.
In humans ERβ is encoded by the ''ESR2''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Function
ERβ is a member of the family of
estrogen receptor
Estrogen receptors (ERs) are proteins found in cell (biology), cells that function as receptor (biochemistry), receptors for the hormone estrogen (17β-estradiol). There are two main classes of ERs. The first includes the intracellular estrogen ...
s and the superfamily of
nuclear receptor
In the field of molecular biology, nuclear receptors are a class of proteins responsible for sensing steroids, thyroid hormones, vitamins, and certain other molecules. These intracellular receptors work with other proteins to regulate the ex ...
transcription factors. The gene product contains an
N-terminal
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...
DNA binding domain and
C-terminal
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When t ...
ligand binding domain and is localized to the nucleus, cytoplasm, and mitochondria. Upon binding to 17-β-estradiol, estriol or related ligands, the encoded protein forms homo-dimers or hetero-dimers with
estrogen receptor α that interact with specific DNA sequences to activate transcription. Some isoforms dominantly inhibit the activity of other estrogen receptor family members. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been fully characterized.
ERβ may inhibit cell proliferation and opposes the actions of ERα in reproductive tissue.
ERβ may also have an important role in adaptive function of the lung during pregnancy.
ERβ is a potent
tumor suppressor
A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell (biology), cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results ...
and plays a crucial role in many cancer types such as
prostate cancer
Prostate cancer is the neoplasm, uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Abnormal growth of the prostate tissue is usually detected through Screening (medicine), screening tests, ...
and
ovarian cancer
Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different ...
.
Mammary gland
ERβ
knockout mice
A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or " knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...
show normal mammary gland development at
puberty
Puberty is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. It is initiated by hormonal signals from the brain to the gonads: the ovaries in a female, the testicles i ...
and are able to
lactate normally.
The mammary glands of adult virgin female mice are indistinguishable from those of age-matched wild-type virgin female mice.
This is in contrast to
ERα
Estrogen receptor alpha (ERα), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is one of two main types of estrogen receptor, a nuclear receptor (mainly found as a chromatin-binding protein)
that is activated by the se ...
knockout mice, in which a complete absence of mammary gland development at puberty and thereafter is observed.
Administration of the
selective ERβ
agonist
An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...
ERB-041
Prinaberel (INN, USAN) (developmental code names ERB-041, WAY-202041) is a synthetic, nonsteroidal, and highly selective agonist of the ERβ subtype of the estrogen receptor. It is used in scientific research to elucidate the role of the ERβ ...
to immature
ovariectomized female rats produced no observable effects in the mammary glands, further indicating that the ERβ is non-
mammotrophic.
Although ERβ is not required for pubertal development of the mammary glands, it may be involved in
terminal differentiation in
pregnancy
Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins.
Conception (biology), Conception usually occurs ...
, and may also be necessary to maintain the organization and differentiation of mammary
epithelium
Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...
in adulthood.
In old female ERβ knockout mice, severe
cystic mammary disease that is similar in appearance to
postmenopausal
Menopause, also known as the climacteric, is the time when menstrual periods permanently stop, marking the end of the reproductive stage for the female human. It typically occurs between the ages of 45 and 55, although the exact timing can ...
mastopathy develops, whereas this does not occur in aged wild-type female mice.
However, ERβ knockout mice are not only deficient in ERβ signaling in the mammary glands, but also have deficient
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 ma ...
exposure due to impairment of
corpora lutea formation.
This complicates attribution of the preceding findings to mammary ERβ signaling.
Selective ERβ agonism with
diarylpropionitrile
Diarylpropionitrile (DPN), also known as 2,3-bis(p-hydroxyphenyl)propionitrile (2,3-BHPPN), is a synthetic, nonsteroidal, and highly selective agonist of ERβ ( IC50 = 15 nM) that is used widely in scientific research to study the function of th ...
(DPN) has been found to counteract the
proliferative effects in the mammary glands of selective ERα agonism with
propylpyrazoletriol
Propylpyrazoletriol (PPT) is a synthetic, nonsteroidal agonist of ERα with 400-fold selectivity over ERβ that is used widely in scientific research to study the function of ERα. Though originally thought to be highly selective for ERα, PPT ha ...
(PPT) in
ovariectomized postmenopausal female rats.
[Song, X. (2014). Estrogen Receptor Beta Is A Negative Regulator Of Mammary Cell Proliferation. Graduate College Dissertations and Theses. 259. https://scholarworks.uvm.edu/graddis/259] Similarly,
overexpression of ERβ via
lentiviral infection
An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...
in mature virgin female rats decreases mammary proliferation.
ERα signaling has proliferative effects in both normal breast and
breast cancer
Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...
cell line
An immortalised cell line is a population of cells from a multicellular organism that would normally not proliferate indefinitely but, due to mutation, have evaded normal cellular senescence and instead can keep undergoing division. The cells ...
s, whereas ERβ has generally
antiproliferative
Cytostasis (cyto – cell; stasis – stoppage) is the inhibition of cell growth and multiplication. Cytostatic refers to a cellular component or medicine that inhibits cell division and induce cell death.
Cytostasis is an important prerequisite ...
effects in such cell lines.
However, ERβ has been found to have proliferative effects in some breast cell lines.
Expression of ERα and ERβ in the mammary gland have been found to vary throughout 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 makes pregnancy possible. The ovarian cycle controls the production and release of eg ...
and in an ovariectomized state in female rats.
Whereas mammary ERα in
rhesus macaque
The rhesus macaque (''Macaca mulatta''), colloquially rhesus monkey, is a species of Old World monkey. There are between six and nine recognised subspecies split between two groups, the Chinese-derived and the Indian-derived. Generally brown or g ...
s is
downregulated in response to increased
estradiol
Estradiol (E2), also called oestrogen, oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible ...
levels, expression of ERβ in the mammary glands is not.
Expression of ERα and ERβ in the mammary glands also differs throughout life in female mice.
Mammary ERα expression is higher and mammary ERβ expression lower in younger female mice, while mammary ERα expression is lower and mammary ERβ expression higher in older female mice as well as in
parous female mice.
Mammary proliferation and estrogen sensitivity is higher in young female mice than in old or parous female mice, particularly during pubertal mammary gland development.
Tissue distribution
ERβ is expressed by many
tissues including the
uterus
The uterus (from Latin ''uterus'', : uteri or uteruses) or womb () is the hollow organ, organ in the reproductive system of most female mammals, including humans, that accommodates the embryonic development, embryonic and prenatal development, f ...
,
blood monocytes and tissue macrophages, colonic and pulmonary epithelial cells and in prostatic epithelium and in malignant counterparts of these tissues. Also, ERβ is found throughout the brain at different concentrations in different neuron clusters.
ERβ is also highly expressed in normal breast epithelium, although its expression declines with cancer progression. ERβ is expressed in all subtypes of breast cancer. Controversy regarding ERβ protein expression has hindered study of ERβ, but highly sensitive monoclonal antibodies have been produced and well-validated to address these issues.
ERβ abnormalities
ERβ function is related to various cardiovascular targets including
ATP-binding cassette transporter A1 (ABCA1) and
apolipoprotein A1 (ApoA-1). Polymorphism may affect ERβ function and lead to altered responses in postmenopausal women receiving
hormone replacement therapy
Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat symptoms associated with female menopause. Effects of menopause can include symptoms such ...
. Abnormalities in gene expression associated with ERβ have also been linked to
autism spectrum disorder
Autism, also known as autism spectrum disorder (ASD), is a neurodevelopmental disorder characterized by differences or difficulties in social communication and interaction, a preference for predictability and routine, sensory processing di ...
.
Disease
Cardiovascular disease
Mutations in ERβ have been shown to influence
cardiomyocytes
Cardiac muscle (also called heart muscle or myocardium) is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall of ...
, the cells that comprise the largest part of the heart, and can lead to an increased risk of
cardiovascular disease
Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina, heart attack), heart failure, hypertensive heart disease, rheumati ...
(CVD). There is a disparity in prevalence of CVD between pre- and post-menopausal women, and the difference can be attributed to estrogen levels. Many types of ERβ receptors exist in order to help regulate gene expression and subsequent health in the body, but binding of 17βE2 (a naturally occurring estrogen) specifically improves cardiac metabolism. The heart utilizes a lot of energy in the form of
ATP to properly pump blood and maintain physiological requirements in order to live, and 17βE2 helps by increasing these myocardial ATP levels and respiratory function.
In addition, 17βE2 can alter myocardial signaling pathways and stimulate myocyte regeneration, which can aid in inhibiting myocyte cell death. The ERβ signaling pathway plays a role in both
vasodilation
Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. Blood vessel wa ...
and
arterial
An artery () is a blood vessel in humans and most other animals that takes oxygenated blood away from the heart in the systemic circulation to one or more parts of the body. Exceptions that carry deoxygenated blood are the pulmonary arteries in ...
dilation, which contributes to an individual having a healthy heart rate and a decrease in blood pressure. This regulation can increase
endothelial
The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the res ...
function and
arterial perfusion, both of which are important to myocyte health. Thus, alterations in this signaling pathways due to ERβ mutation could lead to myocyte cell death from physiological stress. While ERα has a more profound role in regeneration after myocyte cell death, ERβ can still help by increasing
endothelial progenitor cell
Endothelial progenitor cell (or EPC) is a term that has been applied to multiple different cell types that play roles in the regeneration of the endothelial lining of blood vessels. Outgrowth endothelial cells are an EPC subtype committed to end ...
activation and subsequent cardiac function.
Alzheimer's disease
Genetic variation in ERβ is both sex and age dependent and ERβ polymorphism can lead to accelerated brain aging, cognitive impairment, and development of AD pathology. Similar to CVD, post-menopausal women have an increased risk of developing
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...
(AD) due to a loss of estrogen, which affects proper aging of the
hippocampus
The hippocampus (: hippocampi; via Latin from Ancient Greek, Greek , 'seahorse'), also hippocampus proper, is a major component of the brain of humans and many other vertebrates. In the human brain the hippocampus, the dentate gyrus, and the ...
, neural survival and
regeneration, and
amyloid metabolism. ERβ mRNA is highly expressed in hippocampal formation, an area of the brain that is associated with memory. This expression contributes to increased neuronal survival and helps protect against neurodegenerative diseases such as AD. The pathology of AD is also associated with accumulation of
amyloid beta peptide (Aβ). While a proper concentration of Aβ in the brain is important for healthy functioning, too much can lead to cognitive impairment. Thus, ERβ helps control Aβ levels by maintaining the protein it is derived from, β-amyloid precursor protein. ERβ helps by up-regulating
insulin-degrading enzyme (IDE), which leads to β-amyloid degradation when accumulation levels begin to rise. However, in AD, lack of ERβ causes a decrease in this degradation and an increase in plaque build-up.
ERβ also plays a role in regulating
APOE
Apolipoprotein E (Apo-E) is a protein involved in the metabolism of fats in the body of mammals. A subtype is implicated in Alzheimer's disease and cardiovascular diseases. It is encoded in humans by the gene ''APOE''.
Apo-E belongs to a family ...
, a risk factor for AD that redistributes lipids across cells. APOE expression in the hippocampus is specifically regulated by 17βE2, affecting learning and memory in individuals afflicted with AD. Thus, estrogen therapy via an ERβ-targeted approach can be used as a prevention method for AD either before or at the onset of menopause. Interactions between ERα and ERβ can lead to antagonistic actions in the brain, so an ERβ-targeted approach can increase therapeutic neural responses independently of ERα. Therapeutically, ERβ can be used in both men and women in order to regulate plaque formation in the brain.
Neuroprotective benefits
Synaptic strength and plasticity
ERβ levels can dictate both synaptic strength and
neuroplasticity
Neuroplasticity, also known as neural plasticity or just plasticity, is the ability of neural networks in the brain to change through neurogenesis, growth and reorganization. Neuroplasticity refers to the brain's ability to reorganize and rewir ...
through neural structure modifications. Variations in endogenous estrogen levels cause changes in
dendritic architecture in the hippocampus, which affects neural signaling and plasticity. Specifically, lower estrogen levels lead to decreased dendritic spines and improper signaling, inhibiting plasticity of the brain. However, treatment of 17βE2 can reverse this affect, giving it the ability to modify hippocampal structure. As a result of the relationship between dendritic architecture and
long-term potentiation
In neuroscience, long-term potentiation (LTP) is a persistent strengthening of synapses based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neuron ...
(LTP), ERβ can enhance LTP and lead to an increase in synaptic strength. Furthermore, 17βE2 promotes
neurogenesis
Neurogenesis is the process by which nervous system cells, the neurons, are produced by neural stem cells (NSCs). This occurs in all species of animals except the porifera (sponges) and placozoans. Types of NSCs include neuroepithelial cells ( ...
in developing hippocampal neurons and neurons in the
subventricular zone
The subventricular zone (SVZ) is a region situated on the outside wall of each lateral ventricle of the vertebrate brain. It is present in both the embryonic and adult brain. In embryonic life, the SVZ refers to a secondary proliferative zon ...
and
dentate gyrus
The dentate gyrus (DG) is one of the subfields of the hippocampus, in the hippocampal formation. The hippocampal formation is located in the temporal lobe of the brain, and includes the hippocampus (including CA1 to CA4) subfields, and other su ...
of the adult human brain. Specifically, ERβ increases the proliferation of progenitor cells to create new neurons and can be increased later in life through 17βE2 treatment.
Ligands
Agonists
Non-selective
*
Endogenous
Endogeny, in biology, refers to the property of originating or developing from within an organism, tissue, or cell.
For example, ''endogenous substances'', and ''endogenous processes'' are those that originate within a living system (e.g. an ...
estrogen
Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...
s (e.g.,
estradiol
Estradiol (E2), also called oestrogen, oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible ...
,
estrone
Estrone (E1), also spelled oestrone, is a steroid, a weak estrogen, and a minor female sex hormone. It is one of three major endogenous estrogens, the others being estradiol and estriol. Estrone, as well as the other estrogens, are synthesized ...
,
estriol
Estriol (E3), also spelled oestriol, is a steroid, a weak estrogen, and a minor female sex hormone. It is one of three major endogenous estrogens, the others being estradiol and estrone. Levels of estriol in women who are not pregnant are almost ...
,
estetrol
Estetrol (E4), or oestetrol, is one of the four natural estrogenic steroid hormones found in humans, along with estrone (E1), estradiol (E2), and estriol (E3). Estetrol is a major estrogen in the body. In contrast to estrone and estradiol, estet ...
)
*
Natural
Nature is an inherent character or constitution, particularly of the ecosphere or the universe as a whole. In this general sense nature refers to the laws, elements and phenomena of the physical world, including life. Although humans are part ...
estrogen
Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...
s (e.g.,
conjugated estrogens
Conjugated estrogens (CEs), or conjugated equine estrogens (CEEs), sold under the brand name Premarin among others, is an estrogen medication which is used in menopausal hormone therapy and for various other indications. It is a mixture of th ...
)
*
Synthetic
Synthetic may refer to:
Science
* Synthetic biology
* Synthetic chemical or compound, produced by the process of chemical synthesis
* Synthetic elements, chemical elements that are not naturally found on Earth and therefore have to be created in ...
estrogen
Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...
s (e.g.,
ethinylestradiol
Ethinylestradiol (EE) is an estrogen medication which is used widely in birth control pills in combination with progestins. Ethinylestradiol was widely used for various indications such as the treatment of menopausal symptoms, gynecological ...
,
diethylstilbestrol
Diethylstilbestrol (DES), also known as stilbestrol or stilboestrol, is a nonsteroidal estrogen medication, which is presently rarely used. In the past, it was widely used for a variety of indications, including pregnancy support for those with ...
)
Selective
Agonists of ERβ selective over
ERα
Estrogen receptor alpha (ERα), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is one of two main types of estrogen receptor, a nuclear receptor (mainly found as a chromatin-binding protein)
that is activated by the se ...
include:
*
20-Hydroxyecdysone (ecdysterone, 20-HE, 20-E) —
phytoecdysteroid
Phytoecdysteroids are plant-derived ecdysteroids. Phytoecdysteroids are a class of chemicals that plants synthesize for defense against phytophagous (plant eating) insects. These compounds are mimics of hormones used by arthropods in the molt ...
*
3β-Androstanediol (3β-diol) –
endogenous
Endogeny, in biology, refers to the property of originating or developing from within an organism, tissue, or cell.
For example, ''endogenous substances'', and ''endogenous processes'' are those that originate within a living system (e.g. an ...
*
8β-VE2
*
AC-186
*
Apigenin
Apigenin (4′,5,7-trihydroxyflavone), found in many plants, is a flavone compound that is the aglycone of several naturally occurring glycosides. It is a yellow crystalline solid that has been used to dye wool.
Apigenin is abundant in parsl ...
–
phytoestrogen
A phytoestrogen is a plant-derived xenoestrogen (a type of estrogen produced by organisms other than humans) not generated within the endocrine system, but consumed by eating plants or manufactured foods. Also called a "dietary estrogen", it ...
*
Daidzein
Daidzein (7-hydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one) is a naturally occurring compound found exclusively in soybeans and other legumes, and structurally belongs to a class of compounds known as isoflavones. Daidzein and other isoflavones a ...
– phytoestrogen
*
DCW234
*
Dehydroepiandrosterone
Dehydroepiandrosterone (DHEA), also known as androstenolone, is an endogenous steroid hormone precursor. It is one of the most abundant circulating steroids in humans. DHEA is produced in the adrenal glands, the gonads, and the brain. It funct ...
(DHEA) – endogenous
*
Diarylpropionitrile
Diarylpropionitrile (DPN), also known as 2,3-bis(p-hydroxyphenyl)propionitrile (2,3-BHPPN), is a synthetic, nonsteroidal, and highly selective agonist of ERβ ( IC50 = 15 nM) that is used widely in scientific research to study the function of th ...
(DPN)
*
ERB-79 and its active enantiomer
ERB-26
*
ERB-196
ERB-196, also known as WAY-202196, is a synthetic nonsteroidal estrogen that acts as a highly selective agonist of the ERβ
Estrogen receptor beta (ERβ) also known as NR3A2 (nuclear receptor subfamily 3, group A, member 2) is one of two m ...
(WAY-202196)
*
Erteberel
Erteberel (, ; former developmental code name LY-500307; also known as selective estrogen receptor beta agonist-1 or SERBA-1) is a synthetic, nonsteroidal estrogen which acts as a selective ERβ agonist and was under development by Eli Lilly fo ...
(SERBA-1, LY-500307)
*
FERb 033
FERb 033 is a synthetic, nonsteroidal estrogen that was synthesized in 2009 and is used in scientific research. It is a potent and selective ERβ agonist (Ki = 7.1 nM, EC50 = 4.8 nM), with 62-fold selectivity for the ERβ over the ERα ...
– 62-fold selectivity for ERβ over ERα
*
Genistein
Genistein (C15H10O5) is a plant-derived, aglycone isoflavone. Genistein has the highest content of all isoflavones in soybeans and soy products, such as tempeh. As a type of phytoestrogen, genistein has estrogenic activity in vitro; consequ ...
– phytoestrogen; 16-fold selectivity for ERβ over ERα
*
Liquiritigenin
Liquiritigenin is a flavanone that was isolated from ''Glycyrrhiza uralensis'', and is found in a variety of plants of the Glycyrrhiza genus, including ''Glycyrrhiza glabra'' (licorice). It is an estrogenic compound which acts as a selective agoni ...
(
Menerba
Menerba, also known as Menopause Formula 101 (MF-101), is a botanical drug candidate that acts as a selective estrogen receptor modulator (SERM) which is being studied for its potential to relieve hot flashes associated with menopause. Menerba, an ...
) – phytoestrogen
*
Penduletin – phytoestrogen
*
Prinaberel
Prinaberel (International Nonproprietary Name, INN, United States Adopted Name, USAN) (developmental code names ERB-041, WAY-202041) is a synthetic compound, synthetic, nonsteroidal, and highly binding selectivity, selective agonist of the estrog ...
(ERB-041, WAY-202041)
*
S-Equol
Equol (4',7-isoflavandiol) is an isoflavandiolThe structures of 7,4’-dihydroxy-isoflavan and its precursors is shown iStructural Elucidation of Hydroxylated Metabolites of the Isoflavan Equol by GC/MS and HPLC/MSby Corinna E. Rüfer, Hansruedi G ...
((S)-4',7-isoflavandiol) – phytoestrogen; 13-fold selectivity for ERβ over ERα
*
WAY-166818
*
WAY-200070
WAY-200070 is a synthetic compound, synthetic, nonsteroidal, highly binding selectivity, selective agonist of ERβ. It possesses 68-fold selectivity for ERβ over ERα (EC50, EC50 = 2 nM and 155 nM, respectively). WAY-200070 has been found to enh ...
*
WAY-214156
Antagonists
Non-selective
*
Selective estrogen receptor modulator
Selective estrogen receptor modulators (SERMs), also known as estrogen receptor agonists/antagonists (ERAAs), are a class of drugs that act on estrogen receptors (ERs). Compared to pure ER agonists–antagonists (e.g., full agonists and silent ...
s (e.g.,
tamoxifen
Tamoxifen, sold under the brand name Nolvadex among others, is a selective estrogen receptor modulator used to prevent breast cancer in women and men. It is also being studied for other types of cancer. It has been used for Albright syndrome ...
,
raloxifene)
*
Antiestrogen
Antiestrogens, also known as estrogen antagonists or estrogen blockers, are a class of drugs which prevent estrogens like estradiol from mediating their biological effects in the body. They act by blocking the estrogen receptor (ER) and/or inh ...
s (e.g.,
fulvestrant
Fulvestrant, sold under the brand name Faslodex among others, is an antiestrogenic medication used to treat hormone receptor (HR)-positive metastatic breast cancer in postmenopausal women with disease progression as well as HR-positive, HER2-n ...
,
ICI-164384)
Selective
Antagonists of ERβ selective over ERα include:
*
PHTPP
*
(''R'',''R'')-Tetrahydrochrysene ((''R'',''R'')-THC) – actually not selective over ERα, but rather an agonist instead of antagonist of ERα
Affinities
Interactions
Estrogen receptor beta has been shown to
interact with:
*
CCND1,
*
ESR1
*
MAD2L1
Mitotic spindle assembly checkpoint protein MAD2A is a protein that in humans is encoded by the ''MAD2L1'' gene.
Function
MAD2L1 is a component of the mitotic spindle assembly checkpoint that prevents the onset of anaphase until all chromosome ...
,
[
* NCOA3,]
* NCOA6
Nuclear receptor coactivator 6 is a protein that in humans is encoded by the ''NCOA6'' gene.
Function
The protein encoded by this gene is a transcriptional coactivator that can interact with nuclear hormone receptors to enhance their transc ...
,
* RBM39, and
* SRC.
References
Further reading
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
External links
*
*
{{Estrogen receptor modulators
Intracellular receptors
Transcription factors