GPER1/GPR30 in the brain: Crosstalk with classical estrogen receptors and implications for behavior

Hadjimarkou, Maria M.; Vasudevan, Nandini

doi:10.1016/j.jsbmb.2017.04.012

Cited by 92 publications

(62 citation statements)

References 125 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In particular, we can hypothesise that, with respect to inducing outward and therefore hyperpolarising currents, even if only in a low percentage of cells (25%), GPER1 activation may antagonise excitatory stimuli. In this regard, recent studies have demonstrated that, in different cellular systems, GPER1 and ERα can cross‐talk with each other, highlighting the role of GPER1 as a modulator of classical oestrogen receptors . Indeed, GPER1 signalling appeared to be either synergic or antagonistic for the final output of oestrogenic, ER‐mediated, action .…”

Section: Discussionmentioning

confidence: 99%

The G protein‐coupled oestrogen receptor, GPER1, mediates direct anti‐inflammatory effects of oestrogens in human cholinergic neurones from the nucleus basalis of Meynert

Sarchielli

Guarnieri

Idrizaj

et al. 2020

J Neuroendocrinology

View full text Add to dashboard Cite

It has been well established, particularly in animal models, that oestrogens exert neuroprotective effects in brain areas linked to cognitive processes. A key protective role could reside in the capacity of oestrogen to modulate the inflammatory response. However, the direct neuroprotective actions of oestrogens on neurones are complex and remain to be fully clarified. In the present study, we took advantage of a previously characterised primary culture of human cholinergic neurones (hfNBM) from the foetal nucleus basalis of Meynert, which is known to regulate hippocampal and neocortical learning and memory circuits, aiming to investigate the direct effects of oestrogens under inflammatory conditions. Exposure of cells to tumour necrosis factor (TNF)α (10 ng mL‐1) determined the activation of an inflammatory response, as demonstrated by nuclear factor‐kappa B p65 nuclear translocation and cyclooxygenase‐2 mRNA expression. These effects were inhibited by treatment with either 17β‐oestradiol (E2) (10 nmol L‐1) or G1 (100 nmol L‐1), the selective agonist of the G protein‐coupled oestrogen receptor (GPER1). Interestingly, the GPER1 antagonist G15 abolished the effects of E2 in TNFα‐treated cells, whereas the ERα/ERβ inhibitor tamoxifen did not. Electrophysiological measurements in hfNBMs revealed a depolarising effect caused by E2 that was specifically blocked by tamoxifen and not by G15. Conversely, G1 specifically hyperpolarised the cell membrane and also increased both inward and outward currents elicited by a depolarising stimulus, suggesting a modulatory action on hfNBM excitability by GPER1 activation. Interestingly, pretreating cells with TNFα completely blocked the effects of G1 on membrane properties and also significantly reduced GPER1 mRNA expression. In addition, we found a peculiar subcellular localisation of GPER1 to focal adhesion sites that implicates new possible mechanisms of action of GPER1 in the neuronal perception of mechanical stimuli. The results obtained in the present study indicate a modulatory functional role of GPER1 with respect to mediating the oestrogen neuroprotective effect against inflammation in brain cholinergic neurones and, accordingly, may help to identify protective strategies for preventing cognitive impairments.

show abstract

Section: Discussionmentioning

confidence: 99%

The G protein‐coupled oestrogen receptor, GPER1, mediates direct anti‐inflammatory effects of oestrogens in human cholinergic neurones from the nucleus basalis of Meynert

Sarchielli

Guarnieri

Idrizaj

et al. 2020

J Neuroendocrinology

View full text Add to dashboard Cite

show abstract

“…High levels of ERα expression are also found in the hypothalamus, with particularly elevated expression within the medial preoptic area, as well as the amygdala and ventral medial hypothalamus [ 44 ]. Estrogen and its receptors may improve memory and social behaviors, regulate brain lipid metabolism and prevent cortical damage following an ischemic episode [ 45 – 47 ]. In addition, estrogen and ER are important for bone homeostasis, hepatic lipid metabolism and reverse cholesterol transport [ 48 , 49 ].…”

Section: Expression Of Er In Normal Tissuesmentioning

confidence: 99%

Mechanisms for estrogen receptor expression in human cancer

et al. 2018

View full text Add to dashboard Cite

Estrogen is a steroid hormone that has critical roles in reproductive development, bone homeostasis, cardiovascular remodeling and brain functions. However, estrogen also promotes mammary, ovarian and endometrial tumorigenesis. Estrogen antagonists and drugs that reduce estrogen biosynthesis have become highly successful therapeutic agents for breast cancer patients. The effects of estrogen are largely mediated by estrogen receptor (ER) α and ERβ, which are members of the nuclear receptor superfamily of transcription factors. The mechanisms underlying the aberrant expression of ER in breast cancer and other types of human tumors are complex, involving considerable alternative splicing of ERα and ERβ, transcription factors, epigenetic and post-transcriptional regulation of ER expression. Elucidation of mechanisms for ER expression may not only help understand cancer progression and evolution, but also shed light on overcoming endocrine therapy resistance. Herein, we review the complex mechanisms for regulating ER expression in human cancer.

show abstract

“…In addition, GPER1 activation induces calcium increases which appear to be ryanodine receptor dependent in breast cancer cells (Ariazi et al, 2010). In the brain, GPER1 is implicated in reproductive behavior, social cognition, A C C E P T E D M A N U S C R I P T spatial memory, and neuroprotection (Alexander et al, 2016;Hadjimarkou and Vasudevan, 2018), suggesting that rapid, non-genomic signaling influences these behaviors.…”

Section: The Membrane Er(mer) In the Hypothalamus And Hippocampusmentioning

confidence: 99%