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Research Area
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Description
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Endocrinology |
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Biological Activity
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Description
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Estriol is an antagonist of the G-protein coupled estrogen receptor in estrogen receptor-negative breast cancer cells. |
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Targets
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GPR30 |
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IC50 |
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In Vitro
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MTT assays using G-1 shows that, in SkBr3 cells, the proliferative effect induced by 100 nM G-1 is abolished in the presence of 1 μM estriol which acts as an antagonist of GPR30-dependent pathway. [1]A cell-free transcription assay demonstrates that the antiestrogenic activity exhibited by estriol is because of interferring with estradiol-induced positive cooperative binding and receptor dimerization, binding of hER complexes to ERE, as well as reducing estradiol-dependent transcription in a dose-dependent manner. [2]A recent study shows that estrogen (estrone, estradiol, and estriol) inhibits Alzheimer's disease-associated low-order Aβ oligomer formation, and among them, estriol shows the strongest in vitro activity. [3] |
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In Vivo
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In mPTEN+/- mice, estriol treatments resulted in a 187.54% gain in the relative ratio of uterine wet weight to body weight; estriol also increases the ratio to 176.88% in wild-type mice. [4]Estriol treatment (20 mg/kg ip), in vivo, sensitizes Kupffer cells to LPS via mechanisms dependent on an increase in CD14 by elevated portal blood endotoxin caused by increased gut permeability in rats; while one-half of the rats given estriol intraperitoneally 24 hours before an injection of a sublethal dose of LPS (5 mg/kg) died within 24 hours. [5] |
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Clinical Trials
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Estriol is currently under investigation in Phase I clinical trials; dealing with the vaginal environment of pre-menopausal women. |
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Features
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Protocol
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Cell Assay
[1]
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| Cell Lines |
SkBr3 cells |
| Concentrations |
~100 nM |
| Incubation Time |
6 days |
| Methods |
For the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cells are cultured in plastic 96-well plates under 200 μL of growth medium and at an initial density of 10,000 cells per well. Cells are washed once they have attached and further incubated in medium containing 2.5% charcoal-stripped FBS with the indicated treatment. The medium is changed every 2 days (with treatment). Where applicable, 200 ng of the indicated plasmids are transfected every 2 days before treatments using Fugene6 Reagent, as recommended by the manufacturer. Following 6 days of incubation, the assay mixture (10μL per well) containing 1mg/mL 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) is added to each well and incubated at 37 ?C for 4 h in a 5% CO2 atmosphere. The yellow tetrazolium MTT, reduced by metabolically active cells, results in intracellular purple formazan, which is released after overnight incubation with 200 μL 1% sodium dodecyl sulfate in 0.01N HCL and quantified spectrophotometrically by reading absorbance at 570nm using an enzyme-linked immunosorbent assay plate reader. |
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Animal Study
[4]
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| Animal Models |
mPTEN+/- and wild-type mice |
| Formulation |
Estriol is dissolved in ethanol and corn oil. |
| Doses |
4 μg/g/day |
| Administration |
Administrated via s.c. |
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References |
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[1] Lappano R, et al. Mol Cell Endocrinol. 2010, 320(1-2), 162-170.
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[2] Melamed M, et al. Endocrinol. 1997, 11(12), 1868-1878.
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[3] Morinaga A, et al. Exp Neurol. 2011, 228(2), 298-302.
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[4] Begum M, et al. Lab Invest. 2006,86(3), 286-296.
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[5] Hewitt SC, et al. Environ Health Perspect. 2011, 119(1), 63-70.
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