scholarly journals The Antitumor Peptide ERα17p Exerts Anti-Hyperalgesic and Anti-Inflammatory Actions Through GPER in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Christophe Mallet ◽  
Ludivine Boudieu ◽  
Sylvain Lamoine ◽  
Catherine Coudert ◽  
Yves Jacquot ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Α ◽  
Systemic Administration ◽  
Mice Model ◽  
Persistent Inflammation ◽  
Human Estrogen Receptor ◽  
Anti Inflammatory ◽  
G Protein Coupled ◽  
Inflammatory Action ◽  
Dependent Mechanism

Persistent inflammation and persistent pain are major medical, social and economic burdens. As such, related pharmacotherapy needs to be continuously improved. The peptide ERα17p, which originates from a part of the hinge region/AF2 domain of the human estrogen receptor α (ERα), exerts anti-proliferative effects in breast cancer cells through a mechanism involving the hepta-transmembrane G protein-coupled estrogen receptor (GPER). It is able to decrease the size of xenografted human breast tumors, in mice. As GPER has been reported to participate in pain and inflammation, we were interested in exploring the potential of ERα17p in this respect. We observed that the peptide promoted anti-hyperalgesic effects from 2.5 mg/kg in a chronic mice model of paw inflammation induced by the pro-inflammatory complete Freund’s adjuvant (CFA). This action was abrogated by the specific GPER antagonist G-15, leading to the conclusion that a GPER-dependent mechanism was involved. A systemic administration of a Cy5-labeled version of the peptide allowed its detection in both, the spinal cord and brain. However, ERα17p-induced anti-hyperalgesia was detected at the supraspinal level, exclusively. In the second part of the study, we have assessed the anti-inflammatory action of ERα17p in mice using a carrageenan-evoked hind-paw inflammation model. A systemic administration of ERα17p at a dose of 2.5 mg/kg was responsible for reduced paw swelling. Overall, our work strongly suggests that GPER inverse agonists, including ERα17p, could be used to control hyperalgesia and inflammation.

scholarly journals G protein-coupled estrogen receptor mediates anti-inflammatory action in Crohn’s disease

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Damian Jacenik ◽  
Marta Zielińska ◽  
Anna Mokrowiecka ◽  
Sylwia Michlewska ◽  
Ewa Małecka-Panas ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
G Protein ◽  
Anti Inflammatory ◽  
G Protein Coupled ◽  
Inflammatory Action

scholarly journals Expression of Estrogen Receptor α by Decidual Macrophages in Preeclampsia

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 191 ◽  
Author(s):  
Polina Vishnyakova ◽  
Anastasiya Poltavets ◽  
Maria Nikitina ◽  
Konstantin Midiber ◽  
Liudmila Mikhaleva ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Late Onset ◽  
Normal Pregnancy ◽  
Estrogen Receptor Α ◽  
Control Group ◽  
Tissue Fluid ◽  
Tissue Samples ◽  
Cultural Methods ◽  
Anti Inflammatory ◽  
Early Onset Preeclampsia

Preeclampsia is a gestation-associated hypertensive syndrome that threatens the life and health of the mother and the child. The condition is presumably caused by systemic failure with a strong involvement of innate immunity. In particular, it has been associated with flexible phenotypes of macrophages, which depend on the molecules circulating in the blood and tissue fluid, such as cytokines and hormones. This study aimed at a comparative evaluation of pro-inflammatory (TNFα) and anti-inflammatory (CD206, MMP9, HGF) markers, as well as the levels of estrogen receptor α, expressed by decidual macrophages in normal pregnancy and in patients with early- and late-onset preeclampsia. The tissue samples of decidua basalis were examined by immunohistochemistry and Western blotting. Isolation of decidual macrophages and their characterization were performed using cultural methods, flow cytometry and real-time PCR. Over 50% of the isolated decidual macrophages were positive for the pan-macrophage marker CD68. In the early-onset preeclampsia group, the levels of estrogen receptor α in decidua were significantly decreased. Furthermore, significantly decreased levels of HGF and CD206 were observed in both preeclampsia groups compared with the control group. The observed downregulation of estrogen receptor α, HGF and CD206 may contribute to the balance of pro- and anti-inflammatory macrophages and thereby to pathogenesis of preeclampsia.

scholarly journals Functional characterization of somatic point mutations of the human estrogen receptor α (hERα) in adenomyosis uteri

2004 ◽  
Vol 10 (12) ◽  
pp. 853-860 ◽  
Author(s):  
Martin K. Oehler ◽  
Holger Greschik ◽  
Dagmar-C. Fischer ◽  
Xiaowen Tong ◽  
Roland Schuele ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Functional Characterization ◽  
Point Mutations ◽  
Estrogen Receptor Α ◽  
Human Estrogen Receptor

Biophysical studies of the interaction between calmodulin and the R287-T311 region of human estrogen receptor α reveals an atypical binding process

2012 ◽  
Vol 419 (2) ◽  
pp. 356-361 ◽  
Author(s):  
Ludovic Carlier ◽  
Cillian Byrne ◽  
Emeric Miclet ◽  
Sandrine Bourgoin-Voillard ◽  
Magali Nicaise ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Α ◽  
Binding Process ◽  
Biophysical Studies ◽  
Human Estrogen Receptor

G-protein Coupled Estrogen Receptor Expression in Growth Hormone Secreting and Non-Functioning Adenomas

2020 ◽  
Author(s):  
Hande Mefkure Ozkaya ◽  
Muge Sayitoglu ◽  
Nil Comunoglu ◽  
Eda Sun ◽  
Fatma Ela Keskin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Estrogen Receptor ◽  
Protein Expression ◽  
G Protein ◽  
Estrogen Receptor Α ◽  
Receptor Expression ◽  
Positive Correlation ◽  
Polymerase Chain ◽  
G Protein Coupled ◽  
Transforming Gene

Abstract Purpose To evaluate the expression of G-protein coupled estrogen receptor (GPER1), aromatase, estrogen receptor α (ERα), estrogen receptor β (ERβ), pituitary tumor transforming gene (PTTG), and fibroblast growth factor 2 (FGF2) in GH-secreting and non-functioning adenomas (NFA). Methods Thirty patients with acromegaly and 27 patients with NFA were included. Gene expression was determined via quantitative reverse transcription polymerase chain reaction (QRT-PCR). Protein expression was determined via immunohistochemistry. Results There was no difference, in terms of gene expression of aromatase, ERα, PTTG, and FGF2 between the two groups (p>0.05 for all). ERβ gene expression was higher and GPER1 gene expression was lower in GH-secreting adenomas than NFAs (p<0.05 for all). Aromatase and ERβ protein expression was higher in GH-secreting adenomas than NFAs (p=0.01). None of the tumors expressed ERα. GPER1 expression was detected in 62.2% of the GH-secreting adenomas and 45% of NFAs. There was no difference in terms of GPER1, PTTG, FGF2 H scores between the two groups (p>0.05 for all). GPER1 gene expression was positively correlated to ERα, ERβ, PTTG, and FGF2 gene expression (p<0.05 for all). There was a positive correlation between aromatase and GPER1 protein expression (r=0.31; p=0.04). Conclusions GPER1 is expressed at both gene and protein level in a substantial portion of GH-secreting adenomas and NFAs. The finding of a positive correlation between GPER1 and ERα, ERβ, PTTG, and FGF2 gene expression and aromatase and GPER1 protein expression suggests GPER1 along with aromatase and classical ERs might mediate the effects of estrogen through upregulation of PTTG and FGF2.

Human estrogen receptor α gene is a target of Runx2 transcription factor in osteoblasts

2007 ◽  
Vol 313 (8) ◽  
pp. 1548-1560 ◽  
Author(s):  
Elisabetta Lambertini ◽  
Letizia Penolazzi ◽  
Elisa Tavanti ◽  
Gian Pietro Schincaglia ◽  
Margherita Zennaro ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Transcription Factor ◽  
Estrogen Receptor Α ◽  
Human Estrogen Receptor ◽  
Estrogen Receptor Α Gene
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