Activation of the g protein coupled estrogen receptor

A good fit corresponds with high affinity and low Kd. The final biological response e.

Activation of the g protein coupled estrogen receptor

PDF Abstract Neutrophils are major participants in innate host responses. It is well known that estrogens have an immune-modulatory role, and some evidence exists that neutrophil physiology can be altered by these molecules.

Activation of the g protein coupled estrogen receptor

Traditionally, estrogens act via classical nuclear estrogen receptors, but the identification of a G protein—coupled estrogen receptor GPERa membrane estrogen receptor that binds estradiol and other estrogens, has opened up the possibility of exploring additional estrogen-mediated effects.

However, information on the importance of GPER for immunity, especially, in neutrophils is scant. In this study, we report that gilthead seabream Sparus aurata L.

By using a GPER selective agonist, G1, it was found that GPER activation in vitro slightly reduced the respiratory burst of acidophilic granulocytes and drastically altered the expression profile of several genes encoding major pro- and anti-inflammatory mediators.

In addition, GPER signaling in vivo modulated adaptive immunity. Finally, a cAMP analog mimicked the effects of G1 in the induction of the gene coding for PG-endoperoxide synthase 2 and in the induction of CREB phosphorylation, whereas pharmacological inhibition of protein kinase A superinduced PG-endoperoxide synthase 2.

Introduction It is well known that estrogens have an immune-modulatory role 1. Nevertheless, there are physiological responses to estrogens that cannot be explained by the activation of classical nuclear ER.

Moreover, rapid signaling events initiated by GPER have been shown to regulate gene expression The identification of G1 has allowed the involvement of GPER in several physiological functions to be investigated. For example, GPER has been linked with nervous, reproductive, cardiovascular, and immune systems; metabolism and obesity; cancer and cell growth; and inflammatory vascular diseases, reviewed previously However, information concerning the relevance of GPER for the immune system is scant.

However, it is known that GPER contributes to estrogen-induced thymic atrophy 16 and the impaired production of T cells in the thymus In the context of experimental autoimmune encephalomyelitis EAEGPER knockout mice show impaired estrogen-mediated protection against EAE 18whereas G1 has a beneficial role in multiple sclerosis In addition, G1 is able to promote a suppressive phenotype of CD4 regulatory T cells 20 and is able to induce IL in Th17 effector populations Finally, it has been described that both the affinity and the signaling pathway of GPER are conserved in both mammals and fish Neutrophils play a key role in the innate host response: In response to specific stimuli, neutrophils can synthesize an array of factors such as antimicrobial proteins, extracellular matrix proteins, cytokines, and chemokines, all of which play a major role in early stages of the inflammatory response In the bony fish gilthead seabream Sparus aurata L.

Materials and Methods

AGs might be considered as functionally equivalent to mammalian neutrophils, because they are the most abundant circulating granulocytes 25show strong phagocytic and reactive oxygen species ROS production capabilities 2527produce cytokines in response to several immunological stimuli 2728and express a broad range of TLRs, although not TLR3 In mammals, neutrophil physiology may be altered by estrogens 29 — However, it is unknown whether primary neutrophils express GPER and, if this is the case, what its functional relevance in neutrophil biology is.

In gilthead seabream, AG physiology is also shown to be regulated by estrogens. Despite the massive infiltration of AGs into the testis after spawning 35 — 37they show impaired phagocytic and ROS production activities In the current study, we demonstrate that AGs express a functional GPER, which modulates the gene expression profile and immune activities of these cells after in vitro and in vivo exposure.

The identification of GPER as an important regulator of vertebrate neutrophil biology points to new therapeutic targets for autoimmune diseases where estrogens are involved, such as multiple sclerosis and EAE.

Publication Analysis

The findings are also relevant in the context of endocrine disruption, because xeno-estrogens can activate GPER 42 Materials and Methods Animals, in vivo treatment, and sample collection Healthy specimens of the hermaphroditic protandrous marine fish gilthead seabream Sparus aurata L.

Fish were fasted for 24 h before sampling. The specimens were fed three times per day ad libitum with the G1-containing food for up to 50 d and fasted for 24 h before sampling. To evaluate the effect of G1 on adaptive immunity, the animals were injected i.G protein-coupled estrogen receptor 1 (GPER), also known as G protein-coupled receptor 30 (GPR30), is a protein that in humans is encoded by the GPER gene.

GPER binds to and is activated by the female sex hormone estradiol and is responsible for some of the rapid effects that estradiol has on Chromosome 7 (human). G protein-coupled estrogen receptor 1 mediates acute estrogen-induced cardioprotection via MEK/ERK/GSK-3beta pathway after ischemia/reperfusion.

PLoS One e CrossRef | PubMed | Web of Science® Times Cited: 13; Kilkenny C, Browne W, Cuthill IC, Emerson M, Altman DG (). Animal research: reporting in vivo experiments: the ARRIVE guidelines.

G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein–linked receptors (GPLR), constitute a large protein family of receptors that detect molecules outside the cell and activate internal signal transduction pathways and, ultimately, cellular responses.

Jun 19,  · Keywords: estrogen receptor, G-protein-coupled receptor (GPCR), gene transcription, microRNA (miRNA), microRNA biogenesis, hormones Introduction Dehydroepiandrosterone (DHEA) 4 and its sulfated derivative, DHEA-S, produced in the adrenal (1), is the most abundant endogenous circulating steroid hormone.

G protein-coupled receptors (GPCRs) have been implicated in transmitting signals across the extra- and intra-cellular compartments, thus allowing environmental stimuli to elicit critical biological responses.

Activation of the g protein coupled estrogen receptor

We investigated whether either nuclear or membrane ERs, including G protein-coupled estrogen receptor 1 (Gper1), mediate the inhibitory action of estrogen on insulin-like growth factor-1 (IGF-1)-induced proliferation of pituitary lactotrophs in primary culture.

GPER - Wikipedia