scholarly journals Estetrol: A New Choice for Contraception

2021 ◽  
Vol 10 (23) ◽  
pp. 5625
Author(s):  
Franca Fruzzetti ◽  
Tiziana Fidecicchi ◽  
Maria Magdalena Montt Guevara ◽  
Tommaso Simoncini
Keyword(s):  
Estrogen Receptor ◽  
User Satisfaction ◽  
Large Scale ◽  
Estrogen Receptor Alpha ◽  
Fetal Liver ◽  
Target Population ◽  
Receptor Modulator ◽  
Human Estrogen Receptor ◽  
Synthetic Estrogens ◽  
Orally Bioavailable

Estetrol (E4) is a natural estrogenic steroid that is normally produced by human fetal liver. Recent research has demonstrated that it is a potent, orally bioavailable, natural selective estrogen receptor modulator; it has a moderate affinity for both human estrogen receptor alpha (ERα) and ERβ, with a preference for ERα. Clinical studies have demonstrated possible use as an estrogen in combined oral contraceptives (COC). COCs containing E4 and drospirenone (DRSP) showed a high acceptability, tolerability, and user satisfaction also when compared to COCs containing ethinylestradiol (EE). E4/DRSP effectively inhibits ovulation, with a similar effect on endometrium thickness than that of EE-containing COCs. Low doses (15 mg) of E4 with DRSP (3 mg) showed promising results in term of bleeding pattern and cycle control, also when compared to other COCs containing synthetic estrogens. Moreover, the association has limited effects on serum lipids, liver, SHBG levels, and carbohydrate metabolism. This combination also could drive a lower risk of venous thromboembolism than EE-containing COCs. In this review, we will summarize the actual knowledge about the new E4-containing contraceptive. Further large-scale studies in the full target population are needed to provide more insights into the cardiovascular safety profile and user satisfaction of E4/DRSP.

The transcriptional activities and cellular localization of the human estrogen receptor alpha are affected by the synonymous Ala87 mutation

2014 ◽  
Vol 143 ◽  
pp. 99-104 ◽  
Author(s):  
Tamara Fernández-Calero ◽  
Soledad Astrada ◽  
Álvaro Alberti ◽  
Sofía Horjales ◽  
Jean Francois Arnal ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Cellular Localization ◽  
Estrogen Receptor Alpha ◽  
Receptor Alpha ◽  
Human Estrogen Receptor

scholarly journals Competitive Binding of Some Alkyl p-Hydroxybenzoates to Human Estrogen Receptor α and β

2000 ◽  
Vol 120 (12) ◽  
pp. 1429-1433 ◽  
Author(s):  
Kanako SATOH ◽  
Fumiko NAGAI ◽  
Naoto AOKI ◽  
Motohiro NISHIJIMA
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Alpha ◽  
Competitive Binding ◽  
Receptor Alpha ◽  
Human Estrogen Receptor

A Novel Model of Estrogen Receptor-Positive Breast Cancer Bone Metastasis with Antiestrogen Responsiveness

2021 ◽  
Author(s):  
Kendall L. Langsten ◽  
Lihong Shi ◽  
Adam S. Wilson ◽  
Brian Westwood ◽  
Maria T. Xie ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Bone Metastasis ◽  
Cell Lines ◽  
Triple Negative Breast Cancer ◽  
Estrogen Receptor Alpha ◽  
Triple Negative ◽  
Receptor Alpha ◽  
Ici 182,780 ◽  
Receptor Modulator

AbstractMost women diagnosed with breast cancer (BC) have estrogen receptor alpha positive (ER+) disease. ER+ BC preferentially metastasizes to bone; at which time it is considered incurable. Treatments for bone metastasis have not advanced in decades, in part due to a lack of appropriate ER+ BC bone metastasis models. We developed an immunocompetent ER+ BC murine model with spontaneous bone metastasis and antiestrogen responsiveness. To do this, we transduced triple-negative (TN) bone-tropic murine BC cell lines 4T1.2 and E0771/Bone to express ERα. These cells were then injected into the mammary fat pads of Balb/c (n=21) or C57Bl/6 (n=27), respectively. Once tumors established, mice were treated with either the selective estrogen receptor modulator (SERM) tamoxifen (TAM), the selective estrogen receptor degrader (SERD) ICI 182,780 (ICI, Faslodex, fulvestrant), or vehicle control for 21 days. Tumor volumes and weights significantly decreased in the ER+ groups treated with TAM and ICI compared with ER+ vehicle-treated groups. Staining for immune profiles and total RNA sequencing demonstrated modified immune cell infiltration between TN and ER-derived tumors. Approximately 25% of the mice with ER+ 4T1.2 tumors developed metastases to long bones while none of the mice with TN tumors developed metastases. This immunocompetent ER+ 4T1.2 BC model may allow for further exploration of ER+ BC bone metastasis mechanisms and for the development of new therapeutics for women diagnosed with bone metastasis from ER+ BC.Simple SummaryEstrogen receptor alpha positive (ER+) breast cancer is the most common subtype of breast cancer. When it metastasizes to bone, it becomes incurable. Little advancement has occurred in the treatment of bone metastasis from ER+ breast cancer, partly due to the lack of animal models. To establish an animal model of ER+ BC, we genetically modified two triple-negative breast cancer cell lines to express ERα and injected the cell lines into murine mammary glands. Mice were treated with standard antiestrogen therapies, the selective estrogen receptor modulator tamoxifen or the selective estrogen receptor degrader ICI 182,780. We found that compared to mice with triple-negative breast cancer, mice with ER+ breast cancer developed bone metastases and were responsive to antiestrogen therapy. This model allows for further exploration of bone metastasis mechanisms and for the development of new therapeutics, translating into improved clinical outcomes for women with bone metastasis from ER+ breast cancer.

scholarly journals Computational Study of Estrogen Receptor-Alpha Antagonist with Three-Dimensional Quantitative Structure-Activity Relationship, Support Vector Regression, and Linear Regression Methods

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Ying-Hsin Chang ◽  
Jun-Yan Chen ◽  
Chiou-Yi Hor ◽  
Yu-Chung Chuang ◽  
Chang-Biau Yang ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Inhibitory Activity ◽  
Estrogen Receptor Alpha ◽  
Computational Study ◽  
Three Dimensional ◽  
Quantitative Structure Activity Relationship ◽  
Structural Features ◽  
Support Vector ◽  
Human Estrogen Receptor ◽  
Qsar Models

Human estrogen receptor (ER) isoforms, ERα and ERβ, have long been an important focus in the field of biology. To better understand the structural features associated with the binding of ERα ligands to ERα and modulate their function, several QSAR models, including CoMFA, CoMSIA, SVR, and LR methods, have been employed to predict the inhibitory activity of 68 raloxifene derivatives. In the SVR and LR modeling, 11 descriptors were selected through feature ranking and sequential feature addition/deletion to generate equations to predict the inhibitory activity toward ERα. Among four descriptors that constantly appear in various generated equations, two agree with CoMFA and CoMSIA steric fields and another two can be correlated to a calculated electrostatic potential of ERα.

Phytoestrogens Induce Differential Estrogen Receptor Alpha- or Beta-Mediated Responses in Transfected Breast Cancer Cells

2005 ◽  
Vol 230 (8) ◽  
pp. 558-568 ◽  
Author(s):  
D. M. Harris ◽  
E. Besselink ◽  
S. M. Henning ◽  
V. L. W. Go ◽  
D. Heber
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Estrogen Receptor Alpha ◽  
Estrogenic Activity ◽  
Mammary Adenocarcinoma ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Human Estrogen Receptor ◽  
17Β Estradiol ◽  
Risk Of Cancer

Increased intake of phytoestrogens may be associated with a lower risk of cancer in the breast and several other sites, although there is controversy surrounding this activity. One of the mechanisms proposed to explain the activity of phytoestrogens is their ability to bind and activate human estrogen receptor a (ERα) and human estrogen receptor β (ERβ). Nine phytoestrogens were tested for their ability to transactivate ERα or ERβ at a range of doses. Mammary adenocarcinoma (MCF-7) cells were co-transfected with either ERα or ERβ, and an estrogen-response element was linked to a luciferase reporter gene. Dose-dependent responses were compared with the endogenous ligand 17β-estradiol. Purified genistein, daidzein, apigenin, and coumestrol showed differential and robust transactivation of ERα- and ERβ-induced transcription, with an up to 100-fold stronger activation of ERβ. Equol, naringenin, and kaempferol were weaker agonists. When activity was evaluated against a background of 0.5 nM 17β-estradiol, the addition of genistein, daidzein, and resveratrol superstimulated the system, while kaempferol and quercetin were antagonists at the highest doses. This transfection assay provides an excellent model to evaluate the activation of ERα and ERβ by different phytoestrogens in a breast cancer context and can be used as a screening bioassay tool to evaluate the estrogenic activity of extracts of herbs and foods.

scholarly journals Probing the origin of estrogen receptor alpha inhibition via large-scale QSAR study

RSC Advances ◽  
2018 ◽  
Vol 8 (21) ◽  
pp. 11344-11356 ◽  
Author(s):  
Naravut Suvannang ◽  
Likit Preeyanon ◽  
Aijaz Ahmad Malik ◽  
Nalini Schaduangrat ◽  
Watshara Shoombuatong ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Inhibitory Activity ◽  
Large Scale ◽  
Estrogen Receptor Alpha ◽  
Qsar Modeling ◽  
Qsar Study ◽  
Receptor Alpha

This study compiles a large, non-redundant set of compounds tested for ERα inhibitory activity and applies QSAR modeling for unveiling the privileged substructures governing the activity.

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