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 sex hormone estrogen. In humans, ERα is encoded by the gene ESR1 (EStrogen Receptor 1).
Structure
The estrogen receptor (ER) is a ligand-activated transcription factor composed of several domains important for hormone binding, DNA binding, and activation of transcription. Alternative splicing results in several ESR1 mRNA transcripts, which differ primarily in their 5-prime untranslated regions. The translated receptors show less variability.
Ligands
Agonists
Non-selective
- Endogenous estrogens (e.g., estradiol, estrone, estriol, estetrol)
- Natural estrogens (e.g., conjugated equine estrogens)
- Synthetic estrogens (e.g., ethinylestradiol, diethylstilbestrol)
Selective
Agonists of ERα selective over ERβ include:
- Propylpyrazoletriol (PPT)
- 16α-LE2 (Cpd1471)
- 16α-IE2
- ERA-63 (ORG-37663)
- SKF-82,958 – also a D1-like receptor full agonist
- (R,R)-Tetrahydrochrysene ((R,R)-THC) – actually not selective over ERβ, but rather an antagonist instead of an agonist of ERβ
Mixed
- Phytoestrogens (e.g., coumestrol, daidzein, genistein, miroestrol)
- Selective estrogen receptor modulators (e.g., tamoxifen, clomifene, raloxifene)
Antagonists
Non-selective
- Antiestrogens (e.g., fulvestrant, ICI-164384, ethamoxytriphetol)
Selective
Antagonists of ERα selective over ERβ include:
- Methylpiperidinopyrazole (MPP)
Affinities
Ligand | Other names | Relative binding affinities (RBA, %)a | Absolute binding affinities (Ki, nM)a | Action | ||
---|---|---|---|---|---|---|
ERα | ERβ | ERα | ERβ | |||
Estradiol | E2; 17β-Estradiol | 100 | 100 | 0.115 (0.04–0.24) | 0.15 (0.10–2.08) | Estrogen |
Estrone | E1; 17-Ketoestradiol | 16.39 (0.7–60) | 6.5 (1.36–52) | 0.445 (0.3–1.01) | 1.75 (0.35–9.24) | Estrogen |
Estriol | E3; 16α-OH-17β-E2 | 12.65 (4.03–56) | 26 (14.0–44.6) | 0.45 (0.35–1.4) | 0.7 (0.63–0.7) | Estrogen |
Estetrol | E4; 15α,16α-Di-OH-17β-E2 | 4.0 | 3.0 | 4.9 | 19 | Estrogen |
Alfatradiol | 17α-Estradiol | 20.5 (7–80.1) | 8.195 (2–42) | 0.2–0.52 | 0.43–1.2 | Metabolite |
16-Epiestriol | 16β-Hydroxy-17β-estradiol | 7.795 (4.94–63) | 50 | ? | ? | Metabolite |
17-Epiestriol | 16α-Hydroxy-17α-estradiol | 55.45 (29–103) | 79–80 | ? | ? | Metabolite |
16,17-Epiestriol | 16β-Hydroxy-17α-estradiol | 1.0 | 13 | ? | ? | Metabolite |
2-Hydroxyestradiol | 2-OH-E2 | 22 (7–81) | 11–35 | 2.5 | 1.3 | Metabolite |
2-Methoxyestradiol | 2-MeO-E2 | 0.0027–2.0 | 1.0 | ? | ? | Metabolite |
4-Hydroxyestradiol | 4-OH-E2 | 13 (8–70) | 7–56 | 1.0 | 1.9 | Metabolite |
4-Methoxyestradiol | 4-MeO-E2 | 2.0 | 1.0 | ? | ? | Metabolite |
2-Hydroxyestrone | 2-OH-E1 | 2.0–4.0 | 0.2–0.4 | ? | ? | Metabolite |
2-Methoxyestrone | 2-MeO-E1 | <0.001–<1 | <1 | ? | ? | Metabolite |
4-Hydroxyestrone | 4-OH-E1 | 1.0–2.0 | 1.0 | ? | ? | Metabolite |
4-Methoxyestrone | 4-MeO-E1 | <1 | <1 | ? | ? | Metabolite |
16α-Hydroxyestrone | 16α-OH-E1; 17-Ketoestriol | 2.0–6.5 | 35 | ? | ? | Metabolite |
2-Hydroxyestriol | 2-OH-E3 | 2.0 | 1.0 | ? | ? | Metabolite |
4-Methoxyestriol | 4-MeO-E3 | 1.0 | 1.0 | ? | ? | Metabolite |
Estradiol sulfate | E2S; Estradiol 3-sulfate | <1 | <1 | ? | ? | Metabolite |
Estradiol disulfate | Estradiol 3,17β-disulfate | 0.0004 | ? | ? | ? | Metabolite |
Estradiol 3-glucuronide | E2-3G | 0.0079 | ? | ? | ? | Metabolite |
Estradiol 17β-glucuronide | E2-17G | 0.0015 | ? | ? | ? | Metabolite |
Estradiol 3-gluc. 17β-sulfate | E2-3G-17S | 0.0001 | ? | ? | ? | Metabolite |
Estrone sulfate | E1S; Estrone 3-sulfate | <1 | <1 | >10 | >10 | Metabolite |
Estradiol benzoate | EB; Estradiol 3-benzoate | 10 | ? | ? | ? | Estrogen |
Estradiol 17β-benzoate | E2-17B | 11.3 | 32.6 | ? | ? | Estrogen |
Estrone methyl ether | Estrone 3-methyl ether | 0.145 | ? | ? | ? | Estrogen |
ent-Estradiol | 1-Estradiol | 1.31–12.34 | 9.44–80.07 | ? | ? | Estrogen |
Equilin | 7-Dehydroestrone | 13 (4.0–28.9) | 13.0–49 | 0.79 | 0.36 | Estrogen |
Equilenin | 6,8-Didehydroestrone | 2.0–15 | 7.0–20 | 0.64 | 0.62 | Estrogen |
17β-Dihydroequilin | 7-Dehydro-17β-estradiol | 7.9–113 | 7.9–108 | 0.09 | 0.17 | Estrogen |
17α-Dihydroequilin | 7-Dehydro-17α-estradiol | 18.6 (18–41) | 14–32 | 0.24 | 0.57 | Estrogen |
17β-Dihydroequilenin | 6,8-Didehydro-17β-estradiol | 35–68 | 90–100 | 0.15 | 0.20 | Estrogen |
17α-Dihydroequilenin | 6,8-Didehydro-17α-estradiol | 20 | 49 | 0.50 | 0.37 | Estrogen |
Δ8-Estradiol | 8,9-Dehydro-17β-estradiol | 68 | 72 | 0.15 | 0.25 | Estrogen |
Δ8-Estrone | 8,9-Dehydroestrone | 19 | 32 | 0.52 | 0.57 | Estrogen |
Ethinylestradiol | EE; 17α-Ethynyl-17β-E2 | 120.9 (68.8–480) | 44.4 (2.0–144) | 0.02–0.05 | 0.29–0.81 | Estrogen |
Mestranol | EE 3-methyl ether | ? | 2.5 | ? | ? | Estrogen |
Moxestrol | RU-2858; 11β-Methoxy-EE | 35–43 | 5–20 | 0.5 | 2.6 | Estrogen |
Methylestradiol | 17α-Methyl-17β-estradiol | 70 | 44 | ? | ? | Estrogen |
Diethylstilbestrol | DES; Stilbestrol | 129.5 (89.1–468) | 219.63 (61.2–295) | 0.04 | 0.05 | Estrogen |
Hexestrol | Dihydrodiethylstilbestrol | 153.6 (31–302) | 60–234 | 0.06 | 0.06 | Estrogen |
Dienestrol | Dehydrostilbestrol | 37 (20.4–223) | 56–404 | 0.05 | 0.03 | Estrogen |
Benzestrol (B2) | – | 114 | ? | ? | ? | Estrogen |
Chlorotrianisene | TACE | 1.74 | ? | 15.30 | ? | Estrogen |
Triphenylethylene | TPE | 0.074 | ? | ? | ? | Estrogen |
Triphenylbromoethylene | TPBE | 2.69 | ? | ? | ? | Estrogen |
Tamoxifen | ICI-46,474 | 3 (0.1–47) | 3.33 (0.28–6) | 3.4–9.69 | 2.5 | SERM |
Afimoxifene | 4-Hydroxytamoxifen; 4-OHT | 100.1 (1.7–257) | 10 (0.98–339) | 2.3 (0.1–3.61) | 0.04–4.8 | SERM |
Toremifene | 4-Chlorotamoxifen; 4-CT | ? | ? | 7.14–20.3 | 15.4 | SERM |
Clomifene | MRL-41 | 25 (19.2–37.2) | 12 | 0.9 | 1.2 | SERM |
Cyclofenil | F-6066; Sexovid | 151–152 | 243 | ? | ? | SERM |
Nafoxidine | U-11,000A | 30.9–44 | 16 | 0.3 | 0.8 | SERM |
Raloxifene | – | 41.2 (7.8–69) | 5.34 (0.54–16) | 0.188–0.52 | 20.2 | SERM |
Arzoxifene | LY-353,381 | ? | ? | 0.179 | ? | SERM |
Lasofoxifene | CP-336,156 | 10.2–166 | 19.0 | 0.229 | ? | SERM |
Ormeloxifene | Centchroman | ? | ? | 0.313 | ? | SERM |
Levormeloxifene | 6720-CDRI; NNC-460,020 | 1.55 | 1.88 | ? | ? | SERM |
Ospemifene | Deaminohydroxytoremifene | 0.82–2.63 | 0.59–1.22 | ? | ? | SERM |
Bazedoxifene | – | ? | ? | 0.053 | ? | SERM |
Etacstil | GW-5638 | 4.30 | 11.5 | ? | ? | SERM |
ICI-164,384 | – | 63.5 (3.70–97.7) | 166 | 0.2 | 0.08 | Antiestrogen |
Fulvestrant | ICI-182,780 | 43.5 (9.4–325) | 21.65 (2.05–40.5) | 0.42 | 1.3 | Antiestrogen |
Propylpyrazoletriol | PPT | 49 (10.0–89.1) | 0.12 | 0.40 | 92.8 | ERα agonist |
16α-LE2 | 16α-Lactone-17β-estradiol | 14.6–57 | 0.089 | 0.27 | 131 | ERα agonist |
16α-Iodo-E2 | 16α-Iodo-17β-estradiol | 30.2 | 2.30 | ? | ? | ERα agonist |
Methylpiperidinopyrazole | MPP | 11 | 0.05 | ? | ? | ERα antagonist |
Diarylpropionitrile | DPN | 0.12–0.25 | 6.6–18 | 32.4 | 1.7 | ERβ agonist |
8β-VE2 | 8β-Vinyl-17β-estradiol | 0.35 | 22.0–83 | 12.9 | 0.50 | ERβ agonist |
Prinaberel | ERB-041; WAY-202,041 | 0.27 | 67–72 | ? | ? | ERβ agonist |
ERB-196 | WAY-202,196 | ? | 180 | ? | ? | ERβ agonist |
Erteberel | SERBA-1; LY-500,307 | ? | ? | 2.68 | 0.19 | ERβ agonist |
SERBA-2 | – | ? | ? | 14.5 | 1.54 | ERβ agonist |
Coumestrol | – | 9.225 (0.0117–94) | 64.125 (0.41–185) | 0.14–80.0 | 0.07–27.0 | Xenoestrogen |
Genistein | – | 0.445 (0.0012–16) | 33.42 (0.86–87) | 2.6–126 | 0.3–12.8 | Xenoestrogen |
Equol | – | 0.2–0.287 | 0.85 (0.10–2.85) | ? | ? | Xenoestrogen |
Daidzein | – | 0.07 (0.0018–9.3) | 0.7865 (0.04–17.1) | 2.0 | 85.3 | Xenoestrogen |
Biochanin A | – | 0.04 (0.022–0.15) | 0.6225 (0.010–1.2) | 174 | 8.9 | Xenoestrogen |
Kaempferol | – | 0.07 (0.029–0.10) | 2.2 (0.002–3.00) | ? | ? | Xenoestrogen |
Naringenin | – | 0.0054 (<0.001–0.01) | 0.15 (0.11–0.33) | ? | ? | Xenoestrogen |
8-Prenylnaringenin | 8-PN | 4.4 | ? | ? | ? | Xenoestrogen |
Quercetin | – | <0.001–0.01 | 0.002–0.040 | ? | ? | Xenoestrogen |
Ipriflavone | – | <0.01 | <0.01 | ? | ? | Xenoestrogen |
Miroestrol | – | 0.39 | ? | ? | ? | Xenoestrogen |
Deoxymiroestrol | – | 2.0 | ? | ? | ? | Xenoestrogen |
β-Sitosterol | – | <0.001–0.0875 | <0.001–0.016 | ? | ? | Xenoestrogen |
Resveratrol | – | <0.001–0.0032 | ? | ? | ? | Xenoestrogen |
α-Zearalenol | – | 48 (13–52.5) | ? | ? | ? | Xenoestrogen |
β-Zearalenol | – | 0.6 (0.032–13) | ? | ? | ? | Xenoestrogen |
Zeranol | α-Zearalanol | 48–111 | ? | ? | ? | Xenoestrogen |
Taleranol | β-Zearalanol | 16 (13–17.8) | 14 | 0.8 | 0.9 | Xenoestrogen |
Zearalenone | ZEN | 7.68 (2.04–28) | 9.45 (2.43–31.5) | ? | ? | Xenoestrogen |
Zearalanone | ZAN | 0.51 | ? | ? | ? | Xenoestrogen |
Bisphenol A | BPA | 0.0315 (0.008–1.0) | 0.135 (0.002–4.23) | 195 | 35 | Xenoestrogen |
Endosulfan | EDS | <0.001–<0.01 | <0.01 | ? | ? | Xenoestrogen |
Kepone | Chlordecone | 0.0069–0.2 | ? | ? | ? | Xenoestrogen |
o,p'-DDT | – | 0.0073–0.4 | ? | ? | ? | Xenoestrogen |
p,p'-DDT | – | 0.03 | ? | ? | ? | Xenoestrogen |
Methoxychlor | p,p'-Dimethoxy-DDT | 0.01 (<0.001–0.02) | 0.01–0.13 | ? | ? | Xenoestrogen |
HPTE | Hydroxychlor; p,p'-OH-DDT | 1.2–1.7 | ? | ? | ? | Xenoestrogen |
Testosterone | T; 4-Androstenolone | <0.0001–<0.01 | <0.002–0.040 | >5000 | >5000 | Androgen |
Dihydrotestosterone | DHT; 5α-Androstanolone | 0.01 (<0.001–0.05) | 0.0059–0.17 | 221–>5000 | 73–1688 | Androgen |
Nandrolone | 19-Nortestosterone; 19-NT | 0.01 | 0.23 | 765 | 53 | Androgen |
Dehydroepiandrosterone | DHEA; Prasterone | 0.038 (<0.001–0.04) | 0.019–0.07 | 245–1053 | 163–515 | Androgen |
5-Androstenediol | A5; Androstenediol | 6 | 17 | 3.6 | 0.9 | Androgen |
4-Androstenediol | – | 0.5 | 0.6 | 23 | 19 | Androgen |
4-Androstenedione | A4; Androstenedione | <0.01 | <0.01 | >10000 | >10000 | Androgen |
3α-Androstanediol | 3α-Adiol | 0.07 | 0.3 | 260 | 48 | Androgen |
3β-Androstanediol | 3β-Adiol | 3 | 7 | 6 | 2 | Androgen |
Androstanedione | 5α-Androstanedione | <0.01 | <0.01 | >10000 | >10000 | Androgen |
Etiocholanedione | 5β-Androstanedione | <0.01 | <0.01 | >10000 | >10000 | Androgen |
Methyltestosterone | 17α-Methyltestosterone | <0.0001 | ? | ? | ? | Androgen |
Ethinyl-3α-androstanediol | 17α-Ethynyl-3α-adiol | 4.0 | <0.07 | ? | ? | Estrogen |
Ethinyl-3β-androstanediol | 17α-Ethynyl-3β-adiol | 50 | 5.6 | ? | ? | Estrogen |
Progesterone | P4; 4-Pregnenedione | <0.001–0.6 | <0.001–0.010 | ? | ? | Progestogen |
Norethisterone | NET; 17α-Ethynyl-19-NT | 0.085 (0.0015–<0.1) | 0.1 (0.01–0.3) | 152 | 1084 | Progestogen |
Norethynodrel | 5(10)-Norethisterone | 0.5 (0.3–0.7) | <0.1–0.22 | 14 | 53 | Progestogen |
Tibolone | 7α-Methylnorethynodrel | 0.5 (0.45–2.0) | 0.2–0.076 | ? | ? | Progestogen |
Δ4-Tibolone | 7α-Methylnorethisterone | 0.069–<0.1 | 0.027–<0.1 | ? | ? | Progestogen |
3α-Hydroxytibolone | – | 2.5 (1.06–5.0) | 0.6–0.8 | ? | ? | Progestogen |
3β-Hydroxytibolone | – | 1.6 (0.75–1.9) | 0.070–0.1 | ? | ? | Progestogen |
Footnotes: a = (1) Binding affinity values are of the format "median (range)" (# (#–#)), "range" (#–#), or "value" (#) depending on the values available. The full sets of values within the ranges can be found in the Wiki code. (2) Binding affinities were determined via displacement studies in a variety of in-vitro systems with labeled estradiol and human ERα and ERβ proteins (except the ERβ values from Kuiper et al. (1997), which are rat ERβ). Sources: See template page. |
Tissue distribution and function
ERα plays a role in the physiological development and function of a variety of organ systems to varying degrees, including the reproductive, central nervous, skeletal, and cardiovascular systems. Accordingly, ERα is widely expressed throughout the body, including the uterus and ovary, male reproductive organs, mammary gland, bone, heart, hypothalamus, pituitary gland, liver, lung, kidney, spleen, and adipose tissue. The development and function of these tissues is disrupted in animal models lacking active ERα genes, such as the ERα knockout mouse (ERKO), providing a preliminary understanding of ERα function at specific target organs.
Uterus and ovary
ERα is essential in the maturation of the female reproductive phenotype. In the absence of ERα, the ERKO mouse develops an adult uterus, indicating that ERα may not mediate the initial growth of the uterus. However, ERα plays a role in the completion of this development, and the subsequent function of the tissue. Activation of ERα is known to trigger cell proliferation in the uterus. The uterus of female ERKO mice is hypoplastic, suggesting that ERα mediates mitosis and differentiation in the uterus in response to estrogen stimulation.
Similarly, prepubertal female ERKO mice develop ovaries that are nearly indistinguishable from those of their wildtype counterparts. However, as the ERKO mice mature they progressively present an abnormal ovarian phenotype in both physiology and function. Specifically, female ERKO mice develop enlarged ovaries containing hemorrhagic follicular cysts, which also lack the corpus luteum, and therefore do not ovulate. This adult ovarian phenotype suggests that in the absence of ERα, estrogen is no longer able to perform negative feedback on the hypothalamus, resulting in chronically elevated LH levels and constant ovarian stimulation. These results identify a pivotal role for ERα in the hypothalamus, in addition to its role in the estrogen-driven maturation through theca and interstitial cells of the ovary.
Male reproductive organs
ERα is similarly essential in the maturation and maintenance of the male reproductive phenotype, as male ERKO mice are infertile and present undersized testes. The integrity of testicular structures of ERKO mice, such as the seminiferous tubules of the testes and the seminiferous epithelium, declines over time. Furthermore, the reproductive performance of male ERKO mice is hindered by abnormalities in sexual physiology and behavior, such as impaired spermatogenesis and loss of intromission and ejaculatory responses.
Mammary gland
Estrogen stimulation of ERα is known to stimulate cell proliferation in breast tissue. ERα is thought to be responsible for pubertal development of the adult phenotype, through mediation of mammary gland response to estrogens. This role is consistent with the abnormalities of female ERKO mice: the epithelial ducts of female ERKO mice fail to grow beyond their pre-pubertal length, and lactational structures do not develop. As a result, the functions of the mammary gland—including both lactation and release of prolactin—are greatly impaired in ERKO mice.
Bone
Though its expression in bone is moderate, ERα is known to be responsible for maintenance of bone integrity. It is hypothesized that estrogen stimulation of ERα may trigger the release of growth factors, such as epidermal growth factor or insulin-like growth factor-1, which in turn regulate bone development and maintenance. Accordingly, male and female ERKO mice exhibit decreased bone length and size.
Brain
Estrogen signaling through ERα appears to be responsible for various aspects of central nervous development, such as synaptogenesis and synaptic remodeling. In the brain, ERα is found in hypothalamus, and preoptic area, and arcuate nucleus, all three of which have been linked to reproductive behavior, and the masculinization of the mouse brain appears to take place through ERα function. Furthermore, studies in models of psychopathology and neurodegenerative disease states suggest that estrogen receptors mediate the neuroprotective role of estrogen in the brain. Finally, ERα appears to mediate positive feedback effects of estrogen on the brain's secretion of GnRH and LH, by way increasing expression of kisspeptin in neurons of the arcuate nucleus and anteroventral periventricular nucleus. Although classical studies have suggested that negative feedback effects of estrogen also operate through ERα, female mice lacking ERα in kisspeptin-expressing neurons continue to demonstrate a degree of negative feedback response.
Clinical significance
Estrogen insensitivity syndrome is a very rare condition characterized by a defective ERα that is insensitive to estrogens. The clinical presentation of a female was observed to include absence of breast development and other female secondary sexual characteristics at puberty, hypoplastic uterus, primary amenorrhea, enlarged multicystic ovaries and associated lower abdominal pain, mild hyperandrogenism (manifested as cystic acne), and delayed bone maturation as well as an increased rate of bone turnover. The clinical presentation in a male was reported to include lack of epiphyseal closure, tall stature, osteoporosis, and poor sperm viability. Both individuals were completely insensitive to exogenous estrogen treatment, even with high doses.
Genetic polymorphisms in the gene encoding the ERα have been associated with breast cancer in women, gynecomastia in men and dysmenorrhea.
In patients with breast cancer, mutations in the gene encoding ERα (ESR1) have been associated with resistance to endocrine therapy, especially aromatase inhibitors.
Coactivators
Coactivators of ER-α include:
Interactions
Estrogen receptor alpha has been shown to interact with:
- AKAP13
- AHR
- BRCA1
- CAV1
- CCNC
- CDC25B
- CEBPB
- COBRA1
- COUP-TFI
- CREBBP
- CRSP3
- Cyclin D1
- DDX17
- DDX5
- DNTTIP2
- EP300
- ESR2
- FOXO1
- GREB1
- GTF2H1
- HSPA1A
- HSPA8
- HSP90AA1
- ISL1
- JARID1A
- MVP
- MED1
- MED12
- MED14
- MED16
- MED24
- MED6
- MGMT
- MNAT1
- MTA1
- NCOA6
- NCOA1
- NCOA2
- NCOA3
- NRIP1
- PDLIM1
- POU4F1
- POU4F2
- PRDM2
- PRMT2
- RBM39
- RNF12
- SAFB
- SAFB2
- SHC1
- SHP
- SMARCA4
- SMARCE1
- SRA1
- Src
- TR2
- TR4
- TDG
- TRIM24 and
- XBP1.
References
Further reading
- McDonnell DP, Norris JD (May 2002). "Connections and regulation of the human estrogen receptor". Science. 296 (5573): 1642–1644. Bibcode:2002Sci...296.1642M. doi:10.1126/science.1071884. PMID 12040178. S2CID 30428909.
- Simoncini T, Fornari L, Mannella P, Varone G, Caruso A, Liao JK, Genazzani AR (November 2002). "Novel non-transcriptional mechanisms for estrogen receptor signaling in the cardiovascular system. Interaction of estrogen receptor alpha with phosphatidylinositol 3-OH kinase". Steroids. 67 (12): 935–939. doi:10.1016/S0039-128X(02)00040-5. PMID 12398989. S2CID 42656927.
- Lannigan DA (January 2003). "Estrogen receptor phosphorylation". Steroids. 68 (1): 1–9. doi:10.1016/S0039-128X(02)00110-1. PMID 12475718. S2CID 23163361.
- Herrington DM (April 2003). "Role of estrogen receptor-alpha in pharmacogenetics of estrogen action". Current Opinion in Lipidology. 14 (2): 145–150. doi:10.1097/00041433-200304000-00005. PMID 12642782. S2CID 74820004.
- Tanaka Y, Sasaki M, Kaneuchi M, Fujimoto S, Dahiya R (April 2003). "Estrogen receptor alpha polymorphisms and renal cell carcinoma--a possible risk". Molecular and Cellular Endocrinology. 202 (1–2): 109–116. doi:10.1016/S0303-7207(03)00071-6. PMID 12770739. S2CID 34059244.
- Ali S, Coombes RC (July 2000). "Estrogen receptor alpha in human breast cancer: occurrence and significance". Journal of Mammary Gland Biology and Neoplasia. 5 (3): 271–281. doi:10.1023/A:1009594727358. PMID 14973389. S2CID 23500213.
- Olsson H (July 2000). "Estrogen receptor content in malignant breast tumors in men--a review". Journal of Mammary Gland Biology and Neoplasia. 5 (3): 283–287. doi:10.1023/A:1009546811429. PMID 14973390. S2CID 7342455.
- Surmacz E, Bartucci M (September 2004). "Role of estrogen receptor alpha in modulating IGF-I receptor signaling and function in breast cancer". Journal of Experimental & Clinical Cancer Research. 23 (3): 385–394. PMID 15595626.
- Evinger AJ, Levin ER (2005). "Requirements for estrogen receptor alpha membrane localization and function". Steroids. 70 (5–7): 361–363. doi:10.1016/j.steroids.2005.02.015. PMID 15862818. S2CID 54297122.
- Wang CL, Tang XY, Chen WQ, Su YX, Zhang CX, Chen YM (March 2007). "Association of estrogen receptor alpha gene polymorphisms with bone mineral density in Chinese women: a meta-analysis". Osteoporosis International. 18 (3): 295–305. doi:10.1007/s00198-006-0239-2. PMID 17089081. S2CID 11168531.
- Keaveney M, Klug J, Gannon F (1992). "Sequence analysis of the 5' flanking region of the human estrogen receptor gene". DNA Sequence. 2 (6): 347–358. doi:10.3109/10425179209020816. PMID 1476547.
- Piva R, Gambari R, Zorzato F, Kumar L, del Senno L (March 1992). "Analysis of upstream sequences of the human estrogen receptor gene". Biochemical and Biophysical Research Communications. 183 (3): 996–1002. doi:10.1016/S0006-291X(05)80289-X. PMID 1567414.
- Reese JC, Katzenellenbogen BS (May 1992). "Characterization of a temperature-sensitive mutation in the hormone binding domain of the human estrogen receptor. Studies in cell extracts and intact cells and their implications for hormone-dependent transcriptional activation". The Journal of Biological Chemistry. 267 (14): 9868–9873. doi:10.1016/S0021-9258(19)50174-0. PMID 1577818.
- Dotzlaw H, Alkhalaf M, Murphy LC (May 1992). "Characterization of estrogen receptor variant mRNAs from human breast cancers". Molecular Endocrinology. 6 (5): 773–785. doi:10.1210/mend.6.5.1603086. PMID 1603086. S2CID 25208340.
- Keaveney M, Klug J, Dawson MT, Nestor PV, Neilan JG, Forde RC, Gannon F (February 1991). "Evidence for a previously unidentified upstream exon in the human oestrogen receptor gene". Journal of Molecular Endocrinology. 6 (1): 111–115. doi:10.1677/jme.0.0060111. PMID 2015052.
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External links
- FactorBook ERalpha_a
- Overview of all the structural information available in the PDB for UniProt: P03372 (Estrogen receptor) at the PDBe-KB.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.