scholarly journals The 17β-estradiol induced upregulation of the adhesion G-protein coupled receptor (ADGRG7) is modulated by ESRα and SP1 complex

Biology Open ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. bio037390 ◽  
Author(s):  
Amani Hassan ◽  
Edward T. Bagu ◽  
Mathieu Levesque ◽  
Shunmoogum A. Patten ◽  
Samira Benhadjeba ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptor ◽  
17Β Estradiol ◽  
G Protein Coupled

scholarly journals The G Protein-Coupled Receptor GPR30 Inhibits Human Urothelial Cell Proliferation

Endocrinology ◽  
2008 ◽  
Vol 149 (8) ◽  
pp. 4024-4034 ◽  
Author(s):  
Jian Teng ◽  
Zun-Yi Wang ◽  
Eric R. Prossnitz ◽  
Dale E. Bjorling
Keyword(s):  
Cell Proliferation ◽  
Cyclin D1 ◽  
G Protein ◽  
Small Interfering Rna ◽  
Urothelial Cell ◽  
Urothelial Cells ◽  
G Protein Coupled Receptor ◽  
17Β Estradiol ◽  
Interfering Rna ◽  
G Protein Coupled

We have previously shown that estrogen stimulates cell proliferation in both normal and transformed urothelial cells mainly through activation of the two primary estrogen receptors (ERs), ERα and ERβ. A growing body of evidence suggests that estrogen also initiates nongenomic effects that cannot be explained by activation of primary ERs. In the present study, we observed that urothelial cells express high amounts of GPR30, a G protein-coupled receptor recently identified as a candidate for membrane-associated estrogen binding. Membrane- impermeable bovine serum albumin-conjugated 17β-estradiol and the specific GPR30 agonist G-1 both inhibited urothelial cell proliferation in a concentration-dependent manner. Transient overexpression of GPR30 inhibited 17β-estradiol (E2)-induced cell proliferation. Decreased GPR30 expression caused by specific small interfering RNA increased E2-induced cell proliferation. These results indicate that membrane-associated inhibitory effects of E2 on cell proliferation correlate with abundance of GPR30. Although E2 induced a significant increase in caspase-3/7 activity, G-1 did not, suggesting that the GPR30-mediated inhibitory effect on cell proliferation was not caused by apoptosis. Furthermore, we found that G-1 failed to induce c-fos, c-jun, and cyclin D1 expression, and GPR30 overexpression abolished E2-induced c-fos, c-jun, and cyclin D1 expression. However, inactivation of GPR30 by small interfering RNA increased c-fos, c-jun, and cyclin D1 expression. These results suggest that GPR30-mediated inhibition of urothelial cell proliferation is the result of decreased cyclin D1 by down-regulation of activation protein-1 signaling.

17β-Estradiol induces vasorelaxation in a G-protein-coupled receptor 30-independent manner

2012 ◽  
Vol 385 (9) ◽  
pp. 945-948 ◽  
Author(s):  
Young Mi Seok ◽  
Eun Jin Jang ◽  
Oliver Reiser ◽  
Markus Hager ◽  
In Kyeom Kim
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptor ◽  
Independent Manner ◽  
17Β Estradiol ◽  
G Protein Coupled

scholarly journals The G Protein-Coupled Receptor GPR30 Mediates the Proliferative Effects Induced by 17β-Estradiol and Hydroxytamoxifen in Endometrial Cancer Cells

2006 ◽  
Vol 20 (3) ◽  
pp. 631-646 ◽  
Author(s):  
Adele Vivacqua ◽  
Daniela Bonofiglio ◽  
Anna Grazia Recchia ◽  
Anna Maria Musti ◽  
Didier Picard ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cancer Cells ◽  
G Protein ◽  
Cell Lines ◽  
Phosphatidylinositol 3 Kinase ◽  
G Protein Coupled Receptor ◽  
17Β Estradiol ◽  
Agonistic Activity ◽  
G Protein Coupled ◽  
Phosphatidylinositol 3

Abstract The growth of both normal and transformed epithelial cells of the female reproductive system is stimulated by estrogens, mainly through the activation of estrogen receptor α (ERα), which is a ligand-regulated transcription factor. The selective ER modulator tamoxifen (TAM) has been widely used as an ER antagonist in breast tumor; however, long-term treatment is associated with an increased risk of endometrial cancer. To provide new insights into the potential mechanisms involved in the agonistic activity exerted by TAM in the uterus, we evaluated the potential of 4-hydroxytamoxifen (OHT), the active metabolite of TAM, to transactivate wild-type ERα and its splice variant expressed in Ishikawa and HEC1A endometrial tumor cells, respectively. OHT was able to antagonize only the activation of ERα by 17β-estradiol (E2) in Ishikawa cells, whereas it up-regulated c-fos expression in a rapid manner similar to E2 and independently of ERα in both cell lines. This stimulation occurred through the G protein-coupled receptor named GPR30 and required Src-related and epidermal growth factor receptor tyrosine kinase activities, along with the activation of both ERK1/2 and phosphatidylinositol 3-kinase/AKT pathways. Most importantly, OHT, like E2, stimulated the proliferation of Ishikawa as well as HEC1A cells. Transfecting a GPR30 antisense expression vector in both endometrial cancer cell lines, OHT was no longer able to induce growth effects, whereas the proliferative response to E2 was completely abrogated only in HEC1A cells. Furthermore, in the presence of the inhibitors of MAPK and phosphatidylinositol 3-kinase pathways, PD 98059 and wortmannin, respectively, E2 and OHT did not elicit growth stimulation. Our data demonstrate a new mode of action of E2 and OHT in endometrial cancer cells, contributing to a better understanding of the molecular mechanisms involved in their uterine agonistic activity.

17β-Estradiol, Genistein, and 4-Hydroxytamoxifen Induce the Proliferation of Thyroid Cancer Cells through the G Protein-Coupled Receptor GPR30

2006 ◽  
Vol 70 (4) ◽  
pp. 1414-1423 ◽  
Author(s):  
Adele Vivacqua ◽  
Daniela Bonofiglio ◽  
Lidia Albanito ◽  
Antonio Madeo ◽  
Vittoria Rago ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
G Protein ◽  
G Protein Coupled Receptor ◽  
17Β Estradiol ◽  
G Protein Coupled ◽  
Thyroid Cancer Cells

scholarly journals The Novel Estrogen Receptor, G Protein-Coupled Receptor 30, Mediates the Proliferative Effects Induced by 17β-Estradiol on Mouse Spermatogonial GC-1 Cell Line

Endocrinology ◽  
2008 ◽  
Vol 149 (10) ◽  
pp. 5043-5051 ◽  
Author(s):  
Rosa Sirianni ◽  
Adele Chimento ◽  
Carmen Ruggiero ◽  
Arianna De Luca ◽  
Rosamaria Lappano ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathways ◽  
Cell Line ◽  
G Protein ◽  
Knockout Mice ◽  
Growth Factor Receptor ◽  
Estrogen Signaling ◽  
G Protein Coupled Receptor ◽  
17Β Estradiol ◽  
G Protein Coupled

Many studies have indicated that estrogens could have a role in the regulation of testicular function. However, it remains uncertain whether estrogens are able to directly activate signaling pathways in male germ cells. Estrogens are synthesized by the enzyme aromatase and classically act by binding to estrogen receptors (ERs)-α and ERβ. Knockout mice for both receptor isoforms exhibit a testicular phenotype that is less severe than aromatase knockout mice, suggesting the existence of an estrogen-binding receptor that may compensate for the lack of ERs. Recently studies using estrogen-sensitive tumor cell lines have demonstrated that the G-protein-coupled receptor (GPR)-30 binds and mediates estrogen action through the activation of the epidermal growth factor receptor (EGFR)/ERK/fos transduction pathway. The present study investigated the ability of 17β-estradiol (E2) to activate this pathway in the mouse spermatogonial cell line (GC-1). Using the GC-1 cell line as a model system, we demonstrated that GC-1 cells express GPR30 and ERα but not ERβ. E2, the selective GPR30 agonist G1, and the selective ERα agonist 4,4′,4″-(4-propyl-[1H]pyrazole-1,3,5-triyl) trisphenol activated the rapid ERK1/2-fos signaling cascade. This response was abrogated by the EGFR inhibitor AG1478, ERK inhibitor PD98059 and ER inhibitor ICI 182780, or by silencing GPR30 expression. Moreover, E2 and G1 up-regulated cyclin D1 expression and GC-1 cell proliferation. Our results indicate for the first time that estrogens, through a cross talk between GPR30 and ERα, activate the rapid EGFR/ERK/fos pathway, which in turn stimulate mouse GC-1 cell proliferation. Further studies to elucidate the involvement of rapid estrogen signaling pathways in the regulation of male fertility are warranted.

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