Article

GPR30/GPER1: searching for a role in estrogen physiology.

Unit of Drug Target Discovery, Department of Experimental Medical Science, Lund University, SE-22184 Lund, Sweden.
Trends in Endocrinology and Metabolism (Impact Factor: 8.87). 10/2009; 20(8):409-16. DOI: 10.1016/j.tem.2009.04.006
Source: PubMed

ABSTRACT Estrogens are sex hormones that are central to health and disease in both genders. These hormones have long been recognized to act in complex ways, both through relatively slow genomic mechanisms and via fast non-genomic mechanisms. Several recent in vitro studies suggest that GPR30, or G protein-coupled estrogen receptor 1 (GPER1), is a functional membrane estrogen receptor involved in non-genomic estrogen signaling. However, this function is not universally accepted. Studies concerning the role of GPER1 in vivo are now beginning to appear but with divergent results. In this review we discuss current knowledge on the physiological role of GPER1 in the nervous system as well as in reproduction, metabolism, bone, and in the cardiovascular and immune systems.

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    • "This second ER to be discovered, ERβ, has since been shown to be involved in fertility and ovarian function in the rodent, whereas ERα is crucial for E2-mediated reproductive and sexual physiology and behaviors [129] [130]. The role of the most recently identified ER, GPER1, is not yet fully understood, though it is found throughout the nervous system [124]. "
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    03/2014; %(1):35-50. DOI:10.2478/s13380-014-0209-7
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    • "c o m / l o c a t e / s t e r o i d s taken place with regard to the function of the membrane progesterone receptor [22] [23] [24] [25] [26] [27] and unsolved questions had stimulated research in the field [28] [29] [30] [31]. General questions concerned data obtained utilizing different GPER knock-out models generated by different transgenic techniques that have been reviewed in several articles [32] [33] [34] and did not show a homogenous phenotype under physiological conditions. In fact, some groups used specific transgenic lines to argue in favor or to disprove statements of others with regard to the identity or function of this receptor [20] [21]. "
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    ABSTRACT: Rapid signaling of estrogen involves membrane estrogen receptors (ERs), including membrane subpopulations of ERα and ERβ. In the mid-1990s, several laboratories independently reported the cloning of an orphan G protein-coupled receptor from vascular and cancer cells that was named GPR30. Research published between 2000 and 2005 provided evidence that GPR30 binds and signals via estrogen indicating that this intracellular receptor is involved in rapid, non-genomic estrogen signaling. The receptor has since been designated as the G protein-coupled estrogen receptor (GPER) by the International Union of Pharmacology. The availability of genetic tools such as different lines of GPER knock-out mice, as well as GPER-selective agonists and antagonists has advanced our understanding, but also added some confusion about the new function of this receptor. GPER not only binds estrogens but also other substances, including SERMs, SERDs, and environmental ER activators (endocrine disruptors; xenoestrogens) and also interacts with other proteins. This article represents a summary of a lecture given at the 7(th) International Meeting on Rapid Responses to Steroid Hormones in September 2011 in Axos, Crete, and reviews the current knowledge and questions about GPER-dependent signaling and function. Controversies that have complicated our understanding of GPER, including interactions with human ERα-36 and aldosterone as a potential ligand, will also be discussed.
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    • "These findings further indicate that estradiol downregulates Notch signaling in hippocampal neurons (Figure 2). G protein-coupled receptor 30 (GPR30), also known as G protein-coupled estrogen receptor (GPER), is a putative membrane associated ER (Prossnitz et al., 2008; Olde and Leeb- Lundberg, 2009; Prossnitz and Maggiolini, 2009; Langer et al., 2010). GPR30 seems to be involved in the regulation of Notch signaling in hippocampal neurons, since G1, a ligand of GPR30 that imitates the effects of estradiol in different cell types and tissues (Terasawa et al., 2009; Zhang et al., 2010) also imitates the effect of estradiol on Ngn3 expression in hippocampal neurons (Ruiz-Palmero et al., 2011). "
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