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GPER

From Wikipedia, the free encyclopedia

GPER1
Identifiers
AliasesGPER1, Gper1, 6330420K13Rik, CMKRL2, Ceprl, FEG-1, GPCR-Br, Gper, Gpr30, CEPR, DRY12, LERGU, LERGU2, LyGPR, mER, G protein-coupled estrogen receptor 1
External IDsOMIM: 601805; MGI: 1924104; HomoloGene: 15855; GeneCards: GPER1; OMA:GPER1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

2852

76854

Ensembl

ENSG00000164850

ENSMUSG00000053647

UniProt

Q99527

Q8BMP4

RefSeq (mRNA)

NM_001031682
NM_001039966
NM_001098201
NM_001505

NM_029771

RefSeq (protein)

NP_001035055
NP_001091671
NP_001496

NP_084047

Location (UCSC)Chr 7: 1.08 – 1.09 MbChr 5: 139.41 – 139.41 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5] 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 cells.[6]

Discovery

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The classical estrogen receptors first characterized in 1958[7] are water-soluble proteins located in the interior of cells that are activated by estrogenenic hormones such as estradiol and several of its metabolites such as estrone or estriol. These proteins belong to the nuclear hormone receptor class of transcription factors that regulate gene transcription. Since it takes time for genes to be transcribed into RNA and translated into protein, the effects of estrogens binding to these classical estrogen receptors is delayed. However, estrogens are also known to have effects that are too fast to be caused by regulation of gene transcription.[8] In 2005, it was discovered that a member of the G protein-coupled receptor (GPCR) family, GPR30 also binds with high affinity to estradiol and is responsible in part for the rapid non-genomic actions of estradiol. Based on its ability to bind estradiol, GPR30 was renamed as G protein-coupled estrogen receptor (GPER). GPER is localized in the plasma membrane but is predominantly detected in the endoplasmic reticulum.[9][8]

Ligands

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GPER binds estradiol with high affinity though not other endogenous estrogens, such as estrone or estriol, nor other endogenous steroids, including progesterone, testosterone, and cortisol.[6][9][10][11][12] Although potentially involved in signaling by aldosterone, GPER does not show any detectable binding towards aldosterone.[6][13][14] Niacin and nicotinamide bind to the receptor in vitro with very low affinity.[15][16] CCL18 has been identified as an endogenous antagonist of the GPER.[17] GPER-selective ligands (that do not bind the classical estrogen receptors) include the agonist G-1[18] and the antagonists G15[19] and G36.[20][6]

Agonists

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Antagonists

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Unknown

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Non-ligand

[edit]

Function

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This protein is a member of the rhodopsin-like family of G protein-coupled receptors and is a multi-pass membrane protein that localizes to the plasma membrane. The protein binds estradiol, resulting in intracellular calcium mobilization and synthesis of phosphatidylinositol (3,4,5)-trisphosphate in the nucleus.[9] This protein therefore plays a role in the rapid nongenomic signaling events widely observed following stimulation of cells and tissues with estradiol.[21] The distribution of GPER is well established in the rodent, with high expression observed in the hypothalamus, pituitary gland, adrenal medulla, kidney medulla and developing follicles of the ovary.[22]

Role in cancer

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GPER expression has been studied in cancer using immunohistochemical and transcriptomic approaches, and has been detected in: colon, lung, melanoma, pancreatic, breast,[23] ovarian,[24] and testicular cancer.[25]

Many groups have demonstrated that GPER signaling is tumor suppressive in cancers that are not traditionally hormone responsive, including melanoma, pancreatic, lung and colon cancer.[26][27][28][29] Additionally, many groups have demonstrated that GPER activation is also tumor suppressive in cancers that are classically considered sex hormone responsive, including endometrial cancer, ovarian cancer, prostate cancer, and Leydig cell tumors.[30][31][32][33][34] Although GPER signaling was originally thought to be tumor promoting in some breast cancer models,[35] subsequent reports show that GPER signaling inhibits breast cancer.[36][37][38] Consistent with this, recent studies showed that the presence of GPER protein in human breast cancer tissue correlates with longer survival.[39] In summary, many independent groups have demonstrated that GPER activation may be a therapeutically useful mechanism for a wide range of cancer types.

Linnaeus Therapeutics is currently running NCI clinical trial (NCT04130516) using GPER agonist, LNS8801, as monotherapy and in combination with the immune checkpoint inhibitor, pembrolizumab, for the treatment of multiple solid tumor malignancies. Activation of GPER with LNS8801 has demonstrated efficacy in humans in cutaneous melanoma, uveal melanoma, lung cancer, neuroendocrine cancer, colorectal cancer, and other PD-1 inhibitor refractory cancers.[40][41][42]

Role in normal tissues

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Reproductive tissue

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Estradiol produces cell proliferation in both normal and malignant breast epithelial tissue.[43][44] However, GPER knockout mice show no overt mammary phenotype, unlike ERα knockout mice, but similarly to ERβ knockout mice.[43] This indicates that although GPER and ERβ play a modulatory role in breast development, ERα is the main receptor responsible for estrogen-mediated breast tissue growth.[43] GPER is expressed in germ cells and has been found to be essential for male fertility, specifically, in spermatogenesis.[45][46][47][48] GPER has been found to modulate gonadotropin-releasing hormone (GnRH) secretion in the hypothalamic-pituitary-gonadal (HPG) axis.[48]

Cardiovascular effects

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GPER is expressed in the blood vessel endothelium and is responsible for vasodilation and as a result, blood pressure lowering effects of 17β-estradiol.[49] GPER also regulates components of the renin–angiotensin system, which also controls blood pressure,[50][51] and is required for superoxide-mediated cardiovascular function and aging.[52]

Central nervous system activity

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GPER and ERα, but not ERβ, have been found to mediate the antidepressant-like effects of estradiol.[53][54][55] Contrarily, activation of GPER has been found to be anxiogenic in mice, while activation of ERβ has been found to be anxiolytic.[56] There is a high expression of GPER, as well as ERβ, in oxytocin neurons in various parts of the hypothalamus, including the paraventricular nucleus and the supraoptic nucleus.[55][57] It is speculated that activation of GPER may be the mechanism by which estradiol mediates rapid effects on the oxytocin system,[55][57] for instance, rapidly increasing oxytocin receptor expression.[58] Estradiol has also been found to increase oxytocin levels and release in the medial preoptic area and medial basal hypothalamus, actions that may be mediated by activation of GPER and/or ERβ.[58] Estradiol, as well as tamoxifen and fulvestrant, have been found to rapidly induce lordosis through activation of GPER in the arcuate nucleus of the hypothalamus of female rats.[59][60]

Metabolic roles

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Female GPER knockout mice display hyperglycemia and impaired glucose tolerance, reduced body growth, and increased blood pressure.[61] Male GPER knockout mice are observed to have increased growth, body fat, insulin resistance and glucose intolerance, dyslipidemia, increased osteoblast function (mineralization), resulting in higher bone mineral density and trabecular bone volume, and persistent growth plate activity resulting in longer bones.[62][63] The GPER-selective agonist G-1 shows therapeutic efficacy in mouse models of obesity and diabetes.[64]

Role in neurological disorders

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GPER is broadly expressed on the nervous system, and GPER activation promotes beneficial effects in several brain disorders.[65] A study suggests that GPER levels were significantly lower in children with ADHD compared to controls.[66]

See also

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000164850 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000053647 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ O'Dowd BF, Nguyen T, Marchese A, Cheng R, Lynch KR, Heng HH, et al. (January 1998). "Discovery of three novel G-protein-coupled receptor genes". Genomics. 47 (2): 310–313. doi:10.1006/geno.1998.5095. PMID 9479505.
  6. ^ a b c d Prossnitz ER, Arterburn JB (July 2015). "International Union of Basic and Clinical Pharmacology. XCVII. G Protein-Coupled Estrogen Receptor and Its Pharmacologic Modulators". Pharmacological Reviews. 67 (3): 505–540. doi:10.1124/pr.114.009712. PMC 4485017. PMID 26023144.
  7. ^ Jensen E (2012). "A conversation with Elwood Jensen. Interview by David D. Moore". Annual Review of Physiology. 74: 1–11. doi:10.1146/annurev-physiol-020911-153327. PMID 21888507. S2CID 196618575.
  8. ^ a b Vrtačnik P, Ostanek B, Mencej-Bedrač S, Marc J (2014). "The many faces of estrogen signaling". Biochemia Medica. 24 (3): 329–342. doi:10.11613/BM.2014.035. PMC 4210253. PMID 25351351.
  9. ^ a b c Revankar CM, Cimino DF, Sklar LA, Arterburn JB, Prossnitz ER (March 2005). "A transmembrane intracellular estrogen receptor mediates rapid cell signaling". Science. 307 (5715): 1625–1630. Bibcode:2005Sci...307.1625R. doi:10.1126/science.1106943. PMID 15705806. S2CID 15789136.
  10. ^ Filardo EJ, Thomas P (October 2005). "GPR30: a seven-transmembrane-spanning estrogen receptor that triggers EGF release". Trends in Endocrinology and Metabolism. 16 (8): 362–367. doi:10.1016/j.tem.2005.08.005. PMID 16125968. S2CID 33801811.
  11. ^ Manavathi B, Kumar R (June 2006). "Steering estrogen signals from the plasma membrane to the nucleus: two sides of the coin". Journal of Cellular Physiology. 207 (3): 594–604. doi:10.1002/jcp.20551. PMID 16270355. S2CID 27712910.
  12. ^ Prossnitz ER, Arterburn JB, Sklar LA (February 2007). "GPR30: A G protein-coupled receptor for estrogen". Molecular and Cellular Endocrinology. 265–266: 138–142. doi:10.1016/j.mce.2006.12.010. PMC 1847610. PMID 17222505.
  13. ^ Wendler A, Albrecht C, Wehling M (August 2012). "Nongenomic actions of aldosterone and progesterone revisited". Steroids. 77 (10): 1002–1006. doi:10.1016/j.steroids.2011.12.023. PMID 22285849. S2CID 28968323.
  14. ^ Cheng SB, Dong J, Pang Y, LaRocca J, Hixon M, Thomas P, et al. (February 2014). "Anatomical location and redistribution of G protein-coupled estrogen receptor-1 during the estrus cycle in mouse kidney and specific binding to estrogens but not aldosterone". Molecular and Cellular Endocrinology. 382 (2): 950–959. doi:10.1016/j.mce.2013.11.005. PMID 24239983. S2CID 28896943.
  15. ^ Santolla MF, De Francesco EM, Lappano R, Rosano C, Abonante S, Maggiolini M (July 2014). "Niacin activates the G protein estrogen receptor (GPER)-mediated signalling". Cellular Signalling. 26 (7): 1466–1475. doi:10.1016/j.cellsig.2014.03.011. PMID 24662263. Nicotinic acid, also known as niacin, is the water soluble vitamin B3 used for decades for the treatment of dyslipidemic diseases. Its action is mainly mediated by the G protein-coupled receptor (GPR) 109A; however, certain regulatory effects on lipid levels occur in a GPR109A-independent manner. The amide form of nicotinic acid, named nicotinamide, acts as a vitamin although neither activates the GPR109A nor exhibits the pharmacological properties of nicotinic acid. In the present study, we demonstrate for the first time that nicotinic acid and nicotinamide bind to and activate the GPER-mediated signalling in breast cancer cells and cancer-associated fibroblasts (CAFs)
  16. ^ Barton M (July 2016). "Not lost in translation: Emerging clinical importance of the G protein-coupled estrogen receptor GPER". Steroids. 111: 37–45. doi:10.1016/j.steroids.2016.02.016. PMID 26921679.
  17. ^ Catusse J, Wollner S, Leick M, Schröttner P, Schraufstätter I, Burger M (November 2010). "Attenuation of CXCR4 responses by CCL18 in acute lymphocytic leukemia B cells". Journal of Cellular Physiology. 225 (3): 792–800. doi:10.1002/jcp.22284. PMID 20568229. S2CID 24889239.
  18. ^ Bologa CG, Revankar CM, Young SM, Edwards BS, Arterburn JB, Kiselyov AS, et al. (April 2006). "Virtual and biomolecular screening converge on a selective agonist for GPR30". Nature Chemical Biology. 2 (4): 207–212. doi:10.1038/nchembio775. PMID 16520733. S2CID 2364534.
  19. ^ Dennis MK, Burai R, Ramesh C, Petrie WK, Alcon SN, Nayak TK, et al. (June 2009). "In vivo effects of a GPR30 antagonist". Nature Chemical Biology. 5 (6): 421–427. doi:10.1038/nchembio.168. PMC 2864230. PMID 19430488.
  20. ^ Dennis MK, Field AS, Burai R, Ramesh C, Petrie WK, Bologa CG, et al. (November 2011). "Identification of a GPER/GPR30 antagonist with improved estrogen receptor counterselectivity". The Journal of Steroid Biochemistry and Molecular Biology. 127 (3–5): 358–366. doi:10.1016/j.jsbmb.2011.07.002. PMC 3220788. PMID 21782022.
  21. ^ "Entrez Gene: GPR30 G protein-coupled receptor 30".
  22. ^ Hazell GG, Yao ST, Roper JA, Prossnitz ER, O'Carroll AM, Lolait SJ (August 2009). "Localisation of GPR30, a novel G protein-coupled oestrogen receptor, suggests multiple functions in rodent brain and peripheral tissues". The Journal of Endocrinology. 202 (2): 223–236. doi:10.1677/JOE-09-0066. PMC 2710976. PMID 19420011.
  23. ^ Sjöström M, Hartman L, Grabau D, Fornander T, Malmström P, Nordenskjöld B, et al. (May 2014). "Lack of G protein-coupled estrogen receptor (GPER) in the plasma membrane is associated with excellent long-term prognosis in breast cancer". Breast Cancer Research and Treatment. 145 (1): 61–71. doi:10.1007/s10549-014-2936-4. PMID 24715381. S2CID 10593826.
  24. ^ Smith HO, Arias-Pulido H, Kuo DY, Howard T, Qualls CR, Lee SJ, et al. (September 2009). "GPR30 predicts poor survival for ovarian cancer". Gynecologic Oncology. 114 (3): 465–471. doi:10.1016/j.ygyno.2009.05.015. PMC 2921775. PMID 19501895.
  25. ^ Chevalier N, Vega A, Bouskine A, Siddeek B, Michiels JF, Chevallier D, et al. (2012). "GPR30, the non-classical membrane G protein related estrogen receptor, is overexpressed in human seminoma and promotes seminoma cell proliferation". PLOS ONE. 7 (4): e34672. Bibcode:2012PLoSO...734672C. doi:10.1371/journal.pone.0034672. PMC 3319601. PMID 22496838.
  26. ^ Zhu G, Huang Y, Wu C, Wei D, Shi Y (August 2016). "Activation of G-Protein-Coupled Estrogen Receptor Inhibits the Migration of Human Nonsmall Cell Lung Cancer Cells via IKK-β/NF-κB Signals". DNA and Cell Biology. 35 (8): 434–442. doi:10.1089/dna.2016.3235. PMID 27082459.
  27. ^ Liu Q, Chen Z, Jiang G, Zhou Y, Yang X, Huang H, et al. (May 2017). "Epigenetic down regulation of G protein-coupled estrogen receptor (GPER) functions as a tumor suppressor in colorectal cancer". Molecular Cancer. 16 (1): 87. doi:10.1186/s12943-017-0654-3. PMC 5418684. PMID 28476123.
  28. ^ Fábián M, Rencz F, Krenács T, Brodszky V, Hársing J, Németh K, et al. (September 2017). "Expression of G protein-coupled oestrogen receptor in melanoma and in pregnancy-associated melanoma". Journal of the European Academy of Dermatology and Venereology. 31 (9): 1453–1461. doi:10.1111/jdv.14304. PMID 28467693.
  29. ^ Natale CA, Li J, Zhang J, Dahal A, Dentchev T, Stanger BZ, et al. (17 November 2017). "Author response: Activation of G protein-coupled estrogen receptor signaling inhibits melanoma and improves response to immune checkpoint blockade". eLife. doi:10.7554/elife.31770.017.
  30. ^ Ignatov T, Modl S, Thulig M, Weißenborn C, Treeck O, Ortmann O, et al. (July 2013). "GPER-1 acts as a tumor suppressor in ovarian cancer". Journal of Ovarian Research. 6 (1): 51. doi:10.1186/1757-2215-6-51. PMC 3723961. PMID 23849542.
  31. ^ Lam HM, Ouyang B, Chen J, Ying J, Wang J, Wu CL, et al. (6 October 2014). "Targeting GPR30 with G-1: a new therapeutic target for castration-resistant prostate cancer". Endocrine-Related Cancer. 21 (6): 903–914. doi:10.1530/erc-14-0402. PMC 4233119. PMID 25287069.
  32. ^ Skrzypczak M, Schüler S, Lattrich C, Ignatov A, Ortmann O, Treeck O (November 2013). "G protein-coupled estrogen receptor (GPER) expression in endometrial adenocarcinoma and effect of agonist G-1 on growth of endometrial adenocarcinoma cell lines". Steroids. 78 (11): 1087–1091. doi:10.1016/j.steroids.2013.07.007. PMID 23921077.
  33. ^ Chimento A, Casaburi I, Bartucci M, Patrizii M, Dattilo R, Avena P, et al. (August 2013). "Selective GPER activation decreases proliferation and activates apoptosis in tumor Leydig cells". Cell Death & Disease. 4 (8): e747. doi:10.1038/cddis.2013.275. PMC 3763437. PMID 23907461.
  34. ^ Natale CA, Li J, Pitarresi JR, Norgard RJ, Dentchev T, Capell BC, et al. (9 July 2018). "Pharmacologic Activation of the G Protein-Coupled Estrogen Receptor Inhibits Pancreatic Ductal Adenocarcinoma". Cellular and Molecular Gastroenterology and Hepatology. 10 (4): 868–880.e1. doi:10.1101/365668. PMID 32376419.
  35. ^ Lappano R, Pisano A, Maggiolini M (6 May 2014). "GPER Function in Breast Cancer: An Overview". Frontiers in Endocrinology. 5: 66. doi:10.3389/fendo.2014.00066. PMC 4018520. PMID 24834064.
  36. ^ Wei W, Chen ZJ, Zhang KS, Yang XL, Wu YM, Chen XH, et al. (October 2014). "The activation of G protein-coupled receptor 30 (GPR30) inhibits proliferation of estrogen receptor-negative breast cancer cells in vitro and in vivo". Cell Death & Disease. 5 (10): e1428. doi:10.1038/cddis.2014.398. PMC 4649509. PMID 25275589.
  37. ^ Weißenborn C, Ignatov T, Poehlmann A, Wege AK, Costa SD, Zenclussen AC, et al. (April 2014). "GPER functions as a tumor suppressor in MCF-7 and SK-BR-3 breast cancer cells". Journal of Cancer Research and Clinical Oncology. 140 (4): 663–671. doi:10.1007/s00432-014-1598-2. PMID 24515910.
  38. ^ Weißenborn C, Ignatov T, Ochel HJ, Costa SD, Zenclussen AC, Ignatova Z, et al. (May 2014). "GPER functions as a tumor suppressor in triple-negative breast cancer cells". Journal of Cancer Research and Clinical Oncology. 140 (5): 713–723. doi:10.1007/s00432-014-1620-8. PMID 24553912.
  39. ^ Martin SG, Lebot MN, Sukkarn B, Ball G, Green AR, Rakha EA, et al. (May 2018). "Low expression of G protein-coupled oestrogen receptor 1 (GPER) is associated with adverse survival of breast cancer patients". Oncotarget. 9 (40): 25946–25956. doi:10.18632/oncotarget.25408. PMC 5995224. PMID 29899833.
  40. ^ Shoushtari AN, Chaney MF, Cohen JV, Garyantes T, Lin JJ, Ishizuka JJ, et al. (June 2023). "The effect of LNS8801 alone and in combination with pembrolizumab in patients with metastatic uveal melanoma". Journal of Clinical Oncology. 41 (16_suppl): 9543. doi:10.1200/JCO.2023.41.16_suppl.9543. ISSN 0732-183X.
  41. ^ Rodon J, Chaney MF, Cohen J, Garyantes TK, Ishizuka J, Lin JJ, et al. (October 2023). "1101P The effect of LNS8801 in combination with pembrolizumab in patients with treatment-refractory cutaneous melanoma". Annals of Oncology. 34: S663. doi:10.1016/j.annonc.2023.09.2235. ISSN 0923-7534.
  42. ^ Rodon J, Chaney M, Cohen J, Garyantes T, Lin J, Lorusso P, et al. (November 2022). "759 Phase 1b study of LNS8801 in combination with pembrolizumab in patients with secondary resistance to immune checkpoint inhibitors". Regular and Young Investigator Award Abstracts. BMJ Publishing Group Ltd: A790. doi:10.1136/jitc-2022-sitc2022.0759.
  43. ^ a b c Scaling AL, Prossnitz ER, Hathaway HJ (June 2014). "GPER mediates estrogen-induced signaling and proliferation in human breast epithelial cells and normal and malignant breast". Hormones & Cancer. 5 (3): 146–160. doi:10.1007/s12672-014-0174-1. PMC 4091989. PMID 24718936.
  44. ^ Lappano R, Pisano A, Maggiolini M (2014). "GPER Function in Breast Cancer: An Overview". review. Frontiers in Endocrinology. 5: 66. doi:10.3389/fendo.2014.00066. PMC 4018520. PMID 24834064.
  45. ^ Carreau S, Bouraima-Lelong H, Delalande C (November 2011). "Estrogens: new players in spermatogenesis". Reproductive Biology. 11 (3): 174–193. doi:10.1016/s1642-431x(12)60065-5. PMID 22139333.
  46. ^ Carreau S, Bois C, Zanatta L, Silva FR, Bouraima-Lelong H, Delalande C (October 2011). "Estrogen signaling in testicular cells". Life Sciences. 89 (15–16): 584–587. doi:10.1016/j.lfs.2011.06.004. PMID 21703280.
  47. ^ Carreau S, Bouraima-Lelong H, Delalande C (June 2012). "Estrogen, a female hormone involved in spermatogenesis". Advances in Medical Sciences. 57 (1): 31–36. doi:10.2478/v10039-012-0005-y. PMID 22440937.
  48. ^ a b Chimento A, Sirianni R, Casaburi I, Pezzi V (2014). "Role of estrogen receptors and g protein-coupled estrogen receptor in regulation of hypothalamus-pituitary-testis axis and spermatogenesis". Frontiers in Endocrinology. 5: 1. doi:10.3389/fendo.2014.00001. PMC 3893621. PMID 24474947.
  49. ^ Meyer MR, Amann K, Field AS, Hu C, Hathaway HJ, Kanagy NL, et al. (February 2012). "Deletion of G protein-coupled estrogen receptor increases endothelial vasoconstriction". Hypertension. 59 (2): 507–512. doi:10.1161/HYPERTENSIONAHA.111.184606. PMC 3266468. PMID 22203741. The development of the GPER-selective agonist G-114 has facilitated studies that demonstrate GPER activation induces acute vasodilation and lowers blood pressure in rodents. We18 and others17,19 have shown that acute GPER-mediated vasodilator effects are at least partly endothelium- and NO-dependent.
  50. ^ Lindsey SH, Chappell MC (December 2011). "Evidence that the G protein-coupled membrane receptor GPR30 contributes to the cardiovascular actions of estrogen". Gender Medicine. 8 (6): 343–354. doi:10.1016/j.genm.2011.10.004. PMC 3240864. PMID 22153880.
  51. ^ Han G, Li F, Yu X, White RE (May 2013). "GPER: a novel target for non-genomic estrogen action in the cardiovascular system". Pharmacological Research. 71: 53–60. doi:10.1016/j.phrs.2013.02.008. PMID 23466742.
  52. ^ Meyer MR, Fredette NC, Daniel C, Sharma G, Amann K, Arterburn JB, et al. (November 2016). "Obligatory role for GPER in cardiovascular aging and disease". Science Signaling. 9 (452): ra105. doi:10.1126/scisignal.aag0240. PMC 5124501. PMID 27803283.
  53. ^ Estrada-Camarena E, López-Rubalcava C, Vega-Rivera N, Récamier-Carballo S, Fernández-Guasti A (September 2010). "Antidepressant effects of estrogens: a basic approximation". Behavioural Pharmacology. 21 (5–6): 451–464. doi:10.1097/FBP.0b013e32833db7e9. PMID 20700047. S2CID 205595404.
  54. ^ Dennis MK, Burai R, Ramesh C, Petrie WK, Alcon SN, Nayak TK, et al. (June 2009). "In vivo effects of a GPR30 antagonist". Nature Chemical Biology. 5 (6): 421–427. doi:10.1038/nchembio.168. PMC 2864230. PMID 19430488.
  55. ^ a b c Xu H, Qin S, Carrasco GA, Dai Y, Filardo EJ, Prossnitz ER, et al. (February 2009). "Extra-nuclear estrogen receptor GPR30 regulates serotonin function in rat hypothalamus". Neuroscience. 158 (4): 1599–1607. doi:10.1016/j.neuroscience.2008.11.028. PMC 2747636. PMID 19095043.
  56. ^ Kastenberger I, Lutsch C, Schwarzer C (June 2012). "Activation of the G-protein-coupled receptor GPR30 induces anxiogenic effects in mice, similar to oestradiol". Psychopharmacology. 221 (3): 527–535. doi:10.1007/s00213-011-2599-3. PMC 3350630. PMID 22143579.
  57. ^ a b Choleris E (11 April 2013). Oxytocin, Vasopressin and Related Peptides in the Regulation of Behavior. Cambridge University Press. pp. 10–. ISBN 978-0-521-19035-0.
  58. ^ a b Blaustein JD (8 December 2006). Handbook of Neurochemistry and Molecular Neurobiology: Behavioral Neurochemistry, Neuroendocrinology and Molecular Neurobiology. Springer Science & Business Media. pp. 165–. ISBN 978-0-387-30362-8.
  59. ^ Long N, Serey C, Sinchak K (September 2014). "17β-estradiol rapidly facilitates lordosis through G protein-coupled estrogen receptor 1 (GPER) via deactivation of medial preoptic nucleus μ-opioid receptors in estradiol primed female rats". Hormones and Behavior. 66 (4): 663–666. doi:10.1016/j.yhbeh.2014.09.008. PMC 4254307. PMID 25245158.
  60. ^ Long N, Long B, Mana A, Le D, Nguyen L, Chokr S, et al. (March 2017). "Tamoxifen and ICI 182,780 activate hypothalamic G protein-coupled estrogen receptor 1 to rapidly facilitate lordosis in female rats". Hormones and Behavior. 89: 98–103. doi:10.1016/j.yhbeh.2016.12.013. PMC 5359066. PMID 28063803.
  61. ^ Mårtensson UE, Salehi SA, Windahl S, Gomez MF, Swärd K, Daszkiewicz-Nilsson J, et al. (February 2009). "Deletion of the G protein-coupled receptor 30 impairs glucose tolerance, reduces bone growth, increases blood pressure, and eliminates estradiol-stimulated insulin release in female mice". Endocrinology. 150 (2): 687–698. doi:10.1210/en.2008-0623. PMID 18845638.
  62. ^ Ford J, Hajibeigi A, Long M, Hahner L, Gore C, Hsieh JT, et al. (February 2011). "GPR30 deficiency causes increased bone mass, mineralization, and growth plate proliferative activity in male mice". Journal of Bone and Mineral Research. 26 (2): 298–307. doi:10.1002/jbmr.209. PMC 3179349. PMID 20734455.
  63. ^ Sharma G, Hu C, Brigman JL, Zhu G, Hathaway HJ, Prossnitz ER (November 2013). "GPER deficiency in male mice results in insulin resistance, dyslipidemia, and a proinflammatory state". Endocrinology. 154 (11): 4136–4145. doi:10.1210/en.2013-1357. PMC 3800768. PMID 23970785.
  64. ^ Sharma G, Hu C, Staquicini DI, Brigman JL, Liu M, Mauvais-Jarvis F, et al. (January 2020). "Preclinical efficacy of the GPER-selective agonist G-1 in mouse models of obesity and diabetes". Science Translational Medicine. 12 (528): eaau5956. doi:10.1126/scitranslmed.aau5956. PMC 7083206. PMID 31996464.
  65. ^ Roque C, Mendes-Oliveira J, Duarte-Chendo C, Baltazar G (October 2019). "The role of G protein-coupled estrogen receptor 1 on neurological disorders". Frontiers in Neuroendocrinology. 55: 100786. doi:10.1016/j.yfrne.2019.100786. PMID 31513775. S2CID 202043731.
  66. ^ Sahin N, Altun H, Kurutaş EB, Fındıklı E (May 2018). "Evaluation of estrogen and G protein-coupled estrogen receptor 1 (GPER) levels in drug-naïve patients with attention deficit hyperactivity disorder (ADHD)". Bosnian Journal of Basic Medical Sciences. 18 (2): 126–131. doi:10.17305/bjbms.2018.2942. PMC 5988531. PMID 29659348.
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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