scholarly journals Estrogen treatment decreases matrix metalloproteinase (MMP)-9 in autoimmune demyelinating disease through estrogen receptor alpha (ERα)

2009 ◽  
Vol 89 (10) ◽  
pp. 1076-1083 ◽  
Author(s):  
Stefan M Gold ◽  
Manda V Sasidhar ◽  
Laurie B Morales ◽  
Sienmi Du ◽  
Nancy L Sicotte ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Matrix Metalloproteinase ◽  
Estrogen Receptor Alpha ◽  
Demyelinating Disease ◽  
Estrogen Treatment ◽  
Receptor Alpha

scholarly journals Integration of RNA-seq and Ribosome Profiling to Characterize Transcriptional and Translational Estrogen Responses of Genes in Human Breast Cancer

2020 ◽  
Author(s):  
Siew Woh Choo ◽  
Yu Zhong ◽  
Edward Sendler ◽  
Anton Scott Goustin ◽  
Juan Cai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Estrogen Receptor Alpha ◽  
Ribosome Profiling ◽  
Estrogen Treatment ◽  
Differentially Expressed ◽  
Significant Advance ◽  
Rna Seq ◽  
Protein Coding ◽  
Receptor Alpha

Abstract BackgroundEstrogen is a hormone that is frequently essential in breast cancer to drive key transcriptional programs by interacting with the estrogen receptor alpha that upregulates proliferative and oncogenic genes and represses apoptotic and tumor suppressor genes. Protein-coding targets of estrogen regulation in breast cancer are well-defined. However, long non-coding RNA (lncRNA) genes account for the majority of human gene catalogs. The coding status of these genes – their accidental, or regulated, translation by ribosomes, under the influence of estrogen – remains a controversial topic. MethodsHere, we performed comprehensive transcriptome analysis using RNA-Seq, as well as ribosome profiling using Ribo-Seq, on the same samples: biological replicates of human estrogen receptor alpha (ERa) positive MCF7 breast cancer cells before and after estrogen treatment. We correlated these two datasets, globally highlighting protein-coding and lncRNA differentially expressed genes and transcripts that were positively as well as negatively responsive to estrogen, separately at the transcriptional level and the translational (as approximated by ribosome binding) level.ResultsOur data showed that some transcripts were more robustly detected in RNA-Seq than in the ribosome-profiling data, and vice versa, suggesting distinct gene-specific estrogen responses at the transcriptional and the translational level, respectively. Certain differentially expressed transcripts may point to the regulation of alternative splicing by estrogen. Several pseudogenes were co- and anti-regulated with their cancer-functional parental genes. Gene ontology analysis highlighted cancer-relevant pathways enriched after estrogen treatment in cells.ConclusionsOur study represents a significant advance in the estrogen receptor biology, because we demonstrated global effects of estrogen on splicing and translation that are distinct from, and not always correlated with, its effects on transcription, and that differ globally for protein-coding and lncRNA genes. We have also highlighted for the first time the transcriptional and translational response of expressed pseudogenes to estrogen, pointing to new perspectives for biomarker and drug-target development for breast cancer in future.

scholarly journals The role of total and cartilage-specific estrogen receptor alpha expression for the ameliorating effect of estrogen treatment on arthritis

2014 ◽  
Vol 16 (4) ◽  
pp. R150 ◽  
Author(s):  
Cecilia Engdahl ◽  
Anna E Börjesson ◽  
Huamei F Forsman ◽  
Annica Andersson ◽  
Alexandra Stubelius ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Alpha ◽  
Estrogen Treatment ◽  
Receptor Alpha ◽  
And Cartilage

Arginine site 264 in murine estrogen receptor alpha is dispensable for the regulation of the skeleton

2020 ◽  
Author(s):  
Karin L. Gustafsson ◽  
Helen H. Farman ◽  
Karin H. Nilsson ◽  
Petra Henning ◽  
Sofia Movérare-Skrtic ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Bone Mass ◽  
Trabecular Bone ◽  
Cortical Thickness ◽  
Intracellular Signaling ◽  
Estrogen Receptor Alpha ◽  
Estrogen Treatment ◽  
Receptor Alpha ◽  
Trabecular Bone Mass

Estrogen protects against bone loss, but is not a suitable treatment due to adverse effects in other tissues. Increased knowledge regarding estrogen signaling in estrogen-responsive tissues is therefore warranted to aid the development of bone-specific estrogen treatments. Estrogen receptor alpha (ERα), the main mediator of estrogenic effects in bone, is widely subjected to posttranslational modifications (PTMs). In vitro studies have shown that methylation at site R260 in the human ERα affects receptor localization and intracellular signaling. The corresponding amino acid R264 in murine ERα has been shown to have a functional role in endothelium in vivo; albeit the methylation of R264 in the murine gene is yet to be empirically demonstrated. The aim of this study was to investigate if R264 in ERα is involved in the regulation of the skeleton in vivo. DXA analysis at three, six, nine, and twelve months of age showed no differences in total body areal BMD between R264A and WT in either female or male mice. Furthermore, analyses using CT demonstrated that trabecular bone mass in tibia and vertebra, and cortical thickness in tibia, were similar between R264A and WT mice. In addition, R264A females displayed a normal estrogen treatment response in trabecular bone mass, as well as in cortical thickness. Furthermore, uterus, thymus, and adipose tissue responded similarly in R264A and WT female mice after estrogen treatment. In conclusion, our novel finding that mutation of R264 in ERα does not affect the regulation of the skeleton, together with the known role of R264 for ERα-mediated endothelial effects, supports the concept that R264 determines tissue specificity of ERα.

scholarly journals Estrogen receptor alpha regulates the expression of adipogenic genes genetically and epigenetically in rat bone marrow-derived mesenchymal stem cells

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12071
Author(s):  
Ceylan V. Bitirim ◽  
Zeynep B. Ozer ◽  
Kamil C. Akcali
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Estrogen Receptor ◽  
Transcription Factors ◽  
Cell Fate ◽  
Estrogen Receptor Alpha ◽  
Adipogenic Differentiation ◽  
Epigenetic Modifications ◽  
Estrogen Treatment ◽  
Receptor Alpha

Regulation of the efficacy of epigenetic modifiers is regarded as an important control mechanism in the determination and differentiation of stem cell fate. Studies are showing that the effect of estrogen is important in the differentiation of mesenchymal stem cells (MSCs) into adipocytes, osteocytes, and chondrocytes. Activation of certain transcription factors and epigenetic modifications in related genes play an active role in the initiation and completion of adipogenic differentiation. Understanding the role of estrogen in diseases such as obesity, which increases with the onset of menopause, will pave the way for more effective use of estrogen as a therapeutic option. Demonstration of the differentiation tendencies of MSCs change in the presence/absence of estrogen, especially the evaluation of reversible epigenetic changes, will provide valuable information for clinical applications. In this study, the effect of estrogen on the expression of genes involved in adipogenic differentiation of MSCs and accompanying epigenetic modifications was investigated. Our results showed that estrogen affects the expression of adipogenesis-related transcription factors such as PPARy, C/EBPα and Adipsin. In addition, after estrogen treatment, increased accumulation of estrogen receptor alpha (ERα) and repressive epigenetic markers such as H3K27me2 and H3K27me3 were observed on the promoter of given transcription factors. By using co-immunoprecipitation experiments we were also able to show that ERα physically interacts with the zeste homolog 2 (EZH2) H3K27 methyltransferase in MSCs. We propose that the increase of H3K27me2 and H3K27me3 markers on adipogenic genes upon estrogen treatment may be mediated by the direct interaction of ERα and EZH2. Taken together, these findings suggest that estrogen has a role as an epigenetic switcher in the regulation of H3K27 methylation leading to suppression of adipogenic differentiation of MSC.

scholarly journals Estrogen Receptor Alpha and Matrix Metalloproteinase 2 Polymorphisms and Age-related Maculopathy in Older Women

2008 ◽  
Vol 167 (10) ◽  
pp. 1217-1225 ◽  
Author(s):  
R. L. Seitzman ◽  
V. B. Mahajan ◽  
C. Mangione ◽  
J. A. Cauley ◽  
K. E. Ensrud ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Matrix Metalloproteinase ◽  
Older Women ◽  
Estrogen Receptor Alpha ◽  
Matrix Metalloproteinase 2 ◽  
Receptor Alpha ◽  
Age Related

Abstract 397: Transgenic Expression of Cholesteryl Ester Transfer Protein in Female Mice Disrupts Liver and Plasma Triglyceride Metabolism With Estrogen Treatment in a Liver Network Involving Estrogen Receptor Alpha and Small Heterodimer Partner

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Brian T Palmisano ◽  
Lin Zhu ◽  
John M Stafford
Keyword(s):  
Estrogen Receptor ◽  
Cholesteryl Ester ◽  
Mrna Expression ◽  
Estrogen Receptor Alpha ◽  
Estrogen Treatment ◽  
Protein Activity ◽  
Receptor Alpha ◽  
Female Mice ◽  
Transfer Protein ◽  
Small Heterodimer Partner

Background: Triglycerides are an important risk factor for cardiovascular disease, especially in women. Hormone replacement therapy raises triglycerides (TG) in postmenopausal women, but mechanisms responsible remain poorly understood. Cholesteryl Ester Transfer Protein (CETP) is a serum protein that shuttles TG and cholesteryl ester between lipoproteins in humans and plays an important role in lipoprotein metabolism. The role of CETP in regulating whole body triglyceride homeostasis remains unclear. Mice (which naturally lack CETP) expressing a transgenic copy of CETP or their wild-type (WT) littermates were used to determine the role of CETP in regulating plasma and liver TG metabolism in response to estrogen. Methods and Results: Female CETP and WT mice were ovariectomized and given vehicle or estrogen treatment. Estrogen raised plasma TG in CETP females, but not in WT females. CETP expression impaired TG clearance independent of estrogen. Estrogen treatment raised very-low density lipoprotein (VLDL) TG production in CETP females, but not in WT females. Estrogen treatment augmented mRNA expression and protein activity of VLDL assembly and secretion targets (Apob, Mttp, PDI) in CETP females, but not in WT females. Additionally, CETP expression lowered liver TG content and increased mRNA expression of TG oxidation targets (Ppara, Acox1, Acadm, Cpt2). Deletion of liver estrogen receptor alpha prevented CETP-mediated decreases in liver TG content and increases in mRNA expression of TG oxidation targets. Liver-specific deletion of estrogen receptor alpha did not attenuate estrogen-mediated increases in plasma TG and VLDL-TG production in female mice expressing CETP. Deletion of liver small heterodimer partner attenuated CETP-mediated increases in plasma TG and VLDL-TG production with estrogen treatment. Deletion of small heterodimer partner also attenuated CETP-mediated increases in mRNA expression and protein activity of VLDL synthesis and assembly targets with estrogen treatment. Conclusion: These studies indicate several novel functions of CETP in regulating plasma and liver TG homeostasis. We also discovered that CETP expression in female mice also augments several aspects of estrogen action in liver that impact liver TG biology.

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