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: 9.39). 10/2009; 20(8):409-16. DOI: 10.1016/j.tem.2009.04.006
Source: PubMed


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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    ABSTRACT: Studies in both rodents and humans have made much progress in shedding light on how fluctuations in ovarian hormones can affect memory in women across the lifespan. Specifically, advances in neuroscience have identified multiple memory systems that are each mediated by different brain areas. Two memory systems used to navigate an environment are 'place' and 'response' memory. They are defined as either using an allocentric strategy: using a spatial or cognitive map of the surroundings, or an egocentric strategy: using habitual-turns/ movements, respectively. Studies in neuroendocrinology have shown that estrogen levels can bias a female to use one memory system over another to solve a task, such that high estrogen levels are associated with using place memory and low levels with using response memory. Furthermore, recent advances in identifying and localizing estrogen receptors in the rodent brain are uncovering which brain regions are affected by estrogen and providing insight into how hormonal fluctuations during the menstrual cycle, pregnancy, and menopause might affect which memory system is facilitated or impaired in women at different life stages. These studies can help point the way to improving cognitive health in women.
    Full-text · Article · Mar 2014
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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.
    Full-text · Article · Apr 2012 · Steroids
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    • "In the human, GPER (GPR30) has been detected n heart, lung, liver, intestine, ovary, prostate, kidney, brain [11]. In addition, GPER (GPR30)has been also evidenced in neoplastic tissues from breast, endometrial and ovary cancers [12-14] as well as in breast [15-17], endometrial [18,19] ovarian [20] and thyroid carcinoma cells lines [21]. "
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    ABSTRACT: Estrogen signaling is mediated by estrogen receptor beta isoforms in normal and neoplastic human testes. Recently, a G-protein-coupled-receptor (GPER) has been suggested as being involved in rapid responses to estrogens in different normal and tumor cells. This study investigated the GPER expression in paraffin-embedded samples from non neoplastic and neoplastic human testes (sex-cord stromal and germ cell tumors) by immunohistochemical and Western Blot analyses. In control testes, a positive GPER immunoreactivity was detected in Leydig and in Sertoli cells while all germ cells were immunonegative. Furthermore, neoplastic cells of the Sertoli cell tumor, Leydig cell tumor, seminoma and embryonal carcinoma samples were all immunopositive. The immunoblots of testis extracts confirmed the results. These findings suggest that GPER could mediate estrogen signaling in both normal and transformed somatic cells of human testis, but they reveal a differential expression of the novel estrogen receptor in non neoplastic and neoplastic germ cells.
    Full-text · Article · Oct 2011 · Reproductive Biology and Endocrinology
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