ER (Estrogen Receptor) is the receptor of estrogens. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors to mediate ERE-independent signaling[3].
GPR30 (G Protein-Coupled Receptor 30) is a multi-pass membrane protein that localizes to the endoplasmic reticulum. This receptor also binds estrogen and activates multiple downstream signaling pathways. GPR30 plays a role in the rapid nongenomic signaling events widely observed following stimulation of cells and tissues with estrogen. This receptor has been shown to play a role in diverse biological processes[4].
Estradiol is an estrogen that could bind to ER and GPR30. The EC50 reflecting the affinity of estradiol to recombinant human ER was 4×10-8[5]. The growth stimulating EC50 of estradiol on MCF-7 cells was 1.52 μM[6].
Mice were injected intraperitoneally with 100 μl of solution containing 2.5 μg/ml estradiol. Estradiol treatment increased Ki67 staining and mitosis marker phosphor ser10 histone H3 in the uterine epithelial. When estradiol was administrated daily for 3 days, significant increase in uterine weight compared to control group was discovered on the 4th day[7]. In a model of ovariectomized rats, estradiol was subcutaneously injected 2 times at the dose of 10 μg. 2 days following estradiol injection, identical increase in spine density was observed in estradiol-treated mice compared to the control group[8].
Estradiol/17β-雌二醇 细胞实验
Cell Line
Concentration
Treated Time
Description
References
NCM neurons
30 µg/ml
To evaluate the effect of Estradiol on auditory coding in NCM neurons, it was found that Estradiol significantly enhanced the auditory coding efficiency of NCM neurons, increasing their firing rates and information transmission rates.
J Neurosci. 2011 Mar 2;31(9):3271-89.
Estradiol/17β-雌二醇 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
ERα, ERβ, and ERαβ knockout mice
Subcutaneous injection
1, 10, 100, 1000 µg/kg/d
Daily until tissue collection
To determine the role of ERα and ERβ in mediating the protective effects of estradiol on bone mass, results showed that ERα is the main effector of estradiol's protective function in bone, while AR is not sufficient to mediate this response.
J Clin Invest. 2003 May;111(9):1319-27
Rats
Ovariectomized rats
Subcutaneous injection
10 μg
Two injections, 24 hours apart
Estradiol alone facilitated extinction recall
Neuropsychopharmacology. 2016 Feb;41(3):774-80
Zebra finches
Adult zebra finches
Intracerebral injection
30 µg/ml
Initial dose of 100 nl, maintenance doses of 10 nl every 5-10 minutes
To evaluate the effect of Estradiol on auditory coding and song discrimination behavior in zebra finches, it was found that Estradiol significantly enhanced the auditory coding efficiency of NCM neurons and improved the song discrimination behavior of zebra finches.
J Neurosci. 2011 Mar 2;31(9):3271-89.
Mice
ApoE-deficient mice
Subcutaneous implantation
6 µg/day
Once daily for 3 months
To investigate the role of ER α in the atheroprotective effect of E2, results showed that E2 significantly reduced lesion size in AAee mice but had minimal effect in ααee mice lacking ER α.
J Clin Invest. 2001 Feb;107(3):333-40
Arabidopsis thaliana
Arabidopsis wild-type Col-0 and mutants
Treatment in liquid medium
10 μM
24 h (Est) or 16 h (Dex)
To study the cooperative role of CPK5/CPK6 and MPK3/MPK6 in pathogen-induced camalexin biosynthesis
Agonist activity at ERalpha receptor LBD expressed in yeast AH109 cells assessed as interaction with SRC1 after 24 hrs by alpha-galactosidase assay, EC50=1.05 nM
22647217
CHO-K1 cells
Function assay
24 h
Transcriptional activation of ERbeta receptor expressed in CHO-K1 cells after 24 hrs by luciferase reporter gene assay, EC50=3.6e-05 μM
22647217
COS-1 cells
Function assay
In vitro agonist activity for estrogen receptor alpha expressed in COS-1 cells, EC50=2.4 nM
15713407
COS7 cells
Function assay
Displacement of E2-Alexa633 from GFP-tagged ERalpha expressed in COS7 cells by FACS, Ki=0.3 nM
16520733
HEK293 cells
Function assay
Agonist activity at human ERalpha expressed in HEK293 cells by luciferase reporter gene assay, EC50=2.4e-05 μM
25305688
HeLa cells
Function assay
Activation of estrogen response element in HeLa cells stably transfected with human Estrogen receptor alpha, EC50=2e-05 μM
11906280
HepG2 cells
Function assay
24 h
Agonist activity at human ERalpha expressed in HepG2 cells after 24 hrs by luciferase reporter gene assay, EC50=2.2 nM
22283328
human HEC1 cells
Function assay
24 h
Agonist activity at human full-length ERalpha receptor expressed in human HEC1 cells co-expressing (ERE)2-pS2-luc gene assessed as transcriptional activation after 24 hrs by luciferase reporter gene assay, EC50=9e-05 μM
21481497
human Ishikawa cells
Function assay
72 h
Estrogenic activity at estrogen receptor in human Ishikawa cells assessed as induction of alkaline phosphatase expression after 72 hrs by microplate reader, EC50=2.46e-05 μM
22464681
human MCF7 cells
Function assay
6 days
Estrogenic activity in human MCF7 cells assessed as cell proliferation after 6 days by WST8 assay, EC50=3.7e-06 μM
18760603
human SK-BR-3 cells
Function assay
48 h
Inhibition of chemoattractant-induced cell migration of human SK-BR-3 cells after 48 hrs by transwell migration assay, IC50=0.1 nM
16520733
human U2-OS cells
Function assay
Activation of human ERalpha expressed in human U2-OS cells by luciferase reporter gene assay relative to untreated control, EC50=4e-06 μM
23043242
MCF7 cells
Proliferation assay
72 h
Antiproliferative activity against estrogen-deficient human MCF7 cells after 72 hrs by MTT assay, EC50=6.4e-06 μM
22464681
MCF-7 cells
Growth inhibition assay
Growth response in cultures of MCF-7 (human breast cancer cell line) cells, EC50=1.52e-06 μM
9357533
MDA-MB-231 cells
Proliferation assay
2 days
Antiproliferative activity human ER-negative MDA-MB-231 cells after 2 days by MTT assay, IC50=33.46 μM
25222876
SAOS-2 cells
Function assay
Functional Estrogen receptor beta activity by metallothionein induction in SAOS-2 cells, ED50=4.7 nM
12824043
T47D cells
Function assay
Agonist effect on transcriptional activation in T47D cells expressing estrogen receptor alpha, EC50=7e-05 μM
12459017
UAS cells
Function assay
18 h
Agonist activity at ERbeta expressed in UAS cells co-expressing beta-lactamase after 18 hrs by beta-lactamase reporter gene assay, EC50=0.25 nM
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