Evidence Supporting a Role for Gpr30, an Orphan Member of the G-Protein-Coupled Receptor Superfamily, in Rapid Estrogen Signaling

2003 ◽  
pp. 139-146 ◽  
Author(s):  
Edward J. Filardo ◽  
Jeffrey A. Quinn ◽  
C. Thomas Graeber
Keyword(s):  
G Protein ◽  
Estrogen Signaling ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

Estrogen Signaling through the Transmembrane G Protein–Coupled Receptor GPR30

2008 ◽  
Vol 70 (1) ◽  
pp. 165-190 ◽  
Author(s):  
Eric R. Prossnitz ◽  
Jeffrey B. Arterburn ◽  
Harriet O. Smith ◽  
Tudor I. Oprea ◽  
Larry A. Sklar ◽  
...  
Keyword(s):  
G Protein ◽  
Estrogen Signaling ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals The novel estrogen receptor G-protein-coupled receptor 30 is expressed in human bone

2008 ◽  
Vol 197 (2) ◽  
pp. R1-R6 ◽  
Author(s):  
Terhi J Heino ◽  
Andrei S Chagin ◽  
Lars Sävendahl
Keyword(s):  
G Protein ◽  
Bone Cells ◽  
Mineral Metabolism ◽  
Pubertal Development ◽  
Linear Regression Analysis ◽  
Estrogen Signaling ◽  
The Novel ◽  
G Protein Coupled Receptor ◽  
Bone Biopsies ◽  
G Protein Coupled

Estrogens have significant impact on bone mineral metabolism. Besides the classical estrogen receptors (ERα and ERβ), a trans-membrane G-protein-coupled receptor (GPR30) has been demonstrated to mediate estrogenic effects. We aimed to study whether GPR30 is expressed in bone cells and if so, whether the level of expression is developmentally regulated. Metaphyseal bone biopsies were collected from the tibia in 14 boys and 6 girls, all at different stages of puberty. GPR30 protein expression was studied by immunohistochemistry in paraffin-embedded sections. GPR30-positive osteocytes and osteoblasts were quantified and linear regression analysis was applied. Cytoplasmic GPR30 expression was detected in osteoblasts, osteocytes, and osteoclasts. Osteocytes were more frequently positive for GPR30 than osteoblasts (58±4% vs 46±3% positive cells respectively, P<0.05). Detailed analysis demonstrated that GPR30 positivity declined during pubertal development in osteocytes (R=−0.56, P<0.01) but not in osteoblasts (R=−0.31, P>0.05). No sex difference was observed in the numbers of GPR30-positive osteoblasts or osteocytes. Furthermore, GPR30 expression did not correlate with chronological or bone age. In conclusion, the novel ER GPR30 is expressed in osteoblasts, osteocytes, and osteoclasts suggesting that non-genomic estrogen signaling via GPR30 may exist in bone. However, the functional role of GPR30 in bone tissue remains to be elucidated.

scholarly journals Estrogen Signaling Characteristics of Atlantic Croaker G Protein-Coupled Receptor 30 (GPR30) and Evidence It Is Involved in Maintenance of Oocyte Meiotic Arrest

Endocrinology ◽  
2008 ◽  
Vol 149 (7) ◽  
pp. 3410-3426 ◽  
Author(s):  
Yefei Pang ◽  
Jing Dong ◽  
Peter Thomas
Keyword(s):  
G Protein ◽  
Plasma Membranes ◽  
Critical Role ◽  
Hek293 Cells ◽  
Atlantic Croaker ◽  
Estrogen Signaling ◽  
G Protein Coupled Receptor ◽  
Meiotic Arrest ◽  
Transfected Cells ◽  
G Protein Coupled

Human G protein-coupled receptor 30 (GPR30) mediates estradiol-17β (E2) activation of adenylyl cyclase in breast cancer cells and displays E2 binding typical of membrane estrogen receptors (mERs). We identified a mER in Atlantic croaker ovaries with characteristics similar to those of human GPR30. To confirm the proposed role of GPR30 as a mER in this distantly related vertebrate group, we cloned GPR30 from croaker ovaries and examined its distribution, steroid binding, and signaling characteristics. Western blot analysis showed the GPR30 protein (∼40 kDa) is expressed on the plasma membranes of croaker oocytes and HEK293 cells stably transfected with GPR30 cDNA. Plasma membranes prepared from croaker GPR30-transfected cells displayed high-affinity, limited-capacity, and displaceable binding specific for estrogens, characteristic of mERs. Consistent with previous findings with human GPR30, estrogen treatment of plasma membranes from both croaker ovaries and GPR30-transfected cells caused activation of a stimulatory G protein (Gs) resulting in increased cAMP production. Treatment with E2 as well as G-1, a specific GPR30 ligand, significantly reduced both spontaneous and progestin-induced maturation of both croaker and zebrafish oocytes in vitro, suggesting a possible involvement of GPR30 in maintaining oocyte meiotic arrest in these species. Injection of antisense oligonucleotides to GPR30 into zebrafish oocytes blocked the inhibitory effects of estrogen on oocyte maturation, confirming a role for GPR30 in the control of meiotic arrest. These findings further support our previous suggestion that GPR30 is a vertebrate mER. In addition, the results suggest GRP30 may play a critical role in regulating reentry into the meiotic cell cycle in fish oocytes.

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.

Vanadium compounds cause activation of G protein-coupled receptor signaling

2020 ◽  
Author(s):  
Debbie C. Crans ◽  
Duaa Althumairy ◽  
Heide Murakami ◽  
B. George Barisas ◽  
Deborah Roess
Keyword(s):  
G Protein ◽  
Receptor Signaling ◽  
G Protein Coupled Receptor ◽  
Vanadium Compounds ◽  
G Protein Coupled
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