Although the rapid effects of steroids, such as estrogen and aldosterone, were postulated originally to be nongenomic, it is now appreciated that activation of such signaling pathways via a steroid-acting G protein–coupled receptor, the G protein estrogen receptor (GPER), has important transcription-dependent outcomes in the regulation of cell growth and programmed cell death secondary to GPER-regulated second-messenger pathways. GPER is expressed ubiquitously and has diverse biological effects, including regulation of endocrine, immune, neuronal, and cardiovascular functions. Perhaps the most biologically important consequences of GPER activation are the regulation of cell growth, migration, and apoptotic cell death. These cell growth regulatory effects, important in cancer biology, are also relevant in the regulation of cardiac and vascular hypertrophy and in the response to ischemia. This review provides a summary of relevant findings of the impact of GPER regulation by either estradiol or aldosterone in in vitro model systems and extends those findings to in vivo studies of direct clinical relevance for development of GPER-directed agents for treatment of cancer and cardiovascular diseases associated with cellular proliferation.


Article metrics loading...

Loading full text...

Full text loading...


Literature Cited

  1. Cleve A, Fritzemeier KH, Haendler B, Heinrich N, Möller C. 1.  et al. 2012. Pharmacology and clinical use of sex steroid hormone receptor modulators. Handb. Exp. Pharmacol. 214:543–87 [Google Scholar]
  2. Wendler A, Baldi E, Harvey BJ, Nadal A, Norman A, Wehling M. 2.  2010. Position paper: rapid responses to steroids: current status and future prospects. Eur. J. Endocrinol. 162:825–30 [Google Scholar]
  3. Reynolds SR, Foster FI. 3.  1939. Peripheral vascular action of estrogen in the human male. J. Clin. Investig. 18:649–55 [Google Scholar]
  4. Barton M. 4.  2016. Not lost in translation: emerging clinical importance of the G protein-coupled estrogen receptor GPER. Steroids 111:37–45 [Google Scholar]
  5. Streeten DHP, Hirschowitz BI, Henley KS, Pollard HM. 5.  1957. Effects of adrenocortical steroids on the propulsive motility of small intestine. Am. J. Physiol. 189:108–12 [Google Scholar]
  6. Feldman RD, Gros R. 6.  2011. Unraveling the mechanisms underlying the rapid vascular effects of steroids: sorting out the receptors and the pathways. Br. J. Pharmacol. 163:1163–69 [Google Scholar]
  7. Wendler A, Wehling M. 7.  2011. Is GPR30 the membrane aldosterone receptor postulated 20 years ago?. Hypertension 57:e16 [Google Scholar]
  8. Carmeci C, Thompson DA, Ring HZ, Francke U, Weigel RJ. 8.  1997. Identification of a gene (GPR30) with homology to the G-protein-coupled receptor superfamily associated with estrogen receptor expression in breast cancer. Genomics 45:607–17 [Google Scholar]
  9. Takada Y, Kato C, Kondo S, Korenaga R, Ando J. 9.  1997. Cloning of cDNAs encoding G protein-coupled receptor expressed in human endothelial cells exposed to fluid shear stress. Biochem. Biophys. Res. Commun. 240:737–41 [Google Scholar]
  10. Revankar CM, Cimino DF, Sklar LA, Arterburn JB, Prossnitz ER. 10.  2005. A transmembrane intracellular estrogen receptor mediates rapid cell signaling. Science 307:1625–30 [Google Scholar]
  11. Filardo EJ, Quinn JA, Frackelton AR Jr., Bland KI. 11.  2002. Estrogen action via the G protein-coupled receptor, GPR30: stimulation of adenylyl cyclase and cAMP-mediated attenuation of the epidermal growth factor receptor-to-MAPK signaling axis. Mol. Endocrinol. 16:70–84 [Google Scholar]
  12. Filardo E, Quinn J, Pang Y, Graeber C, Shaw S. 12.  et al. 2007. Activation of the novel estrogen receptor G protein-coupled receptor 30 (GPR30) at the plasma membrane. Endocrinology 148:3236–45 [Google Scholar]
  13. Filardo EJ, Thomas P. 13.  2005. GPR30: a seven-transmembrane-spanning estrogen receptor that triggers EGF release. Trends Endocrinol. Metab. 16:362–67 [Google Scholar]
  14. Hasbi A, O'Dowd BF, George SR. 14.  2005. A G protein–coupled receptor for estrogen: the end of the search?. Mol. Interv. 5:158–61 [Google Scholar]
  15. Revankar CM, Mitchell HD, Field AS, Burai R, Corona C. 15.  et al. 2007. Synthetic estrogen derivatives demonstrate the functionality of intracellular GPR30. ACS Chem. Biol. 2:536–44 [Google Scholar]
  16. Vivacqua A, Bonofiglio D, Recchia AG, Musti AM, Picard D. 16.  et al. 2006. The G protein-coupled receptor GPR30 mediates the proliferative effects induced by 17β-estradiol and hydroxytamoxifen in endometrial cancer cells. Mol. Endocrinol. 20:631–46 [Google Scholar]
  17. Wang C, Dehghani B, Magrisso IJ, Rick EA, Bonhomme E. 17.  et al. 2008. GPR30 contributes to estrogen-induced thymic atrophy. Mol. Endocrinol. 22:636–48 [Google Scholar]
  18. Gros R, Ding Q, Sklar LA, Prossnitz EE, Arterburn JB. 18.  et al. 2011. GPR30 expression is required for the mineralocorticoid receptor-independent rapid vascular effects of aldosterone. Hypertension 57:442–51 [Google Scholar]
  19. Ding Q, Gros R, Limbird LE, Chorazyczewski J, Feldman RD. 19.  2009. Estradiol-mediated ERK phosphorylation and apoptosis in vascular smooth muscle cells requires GPR 30. Am. J. Physiol. Cell Physiol. 297:C1178–87 [Google Scholar]
  20. Gros R, Ding Q, Liu B, Chorazyczewski J, Feldman RD. 20.  2013. Aldosterone mediates its rapid effects in vascular endothelial cells through GPER activation. Am. J. Physiol. Cell Physiol. 304:C532–40 [Google Scholar]
  21. Gaudet HM, Cheng SB, Christensen EM, Filardo EJ. 21.  2015. The G-protein coupled estrogen receptor, GPER: the inside and inside-out story. Mol. Cell Endocrinol. 418:Pt. 3207–19 [Google Scholar]
  22. Filardo EJ. 22.  2002. Epidermal growth factor receptor (EGFR) transactivation by estrogen via the G-protein-coupled receptor, GPR30: a novel signaling pathway with potential significance for breast cancer. J. Steroid Biochem. Mol. Biol. 80:231–38 [Google Scholar]
  23. Fujiwara S, Terai Y, Kawaguchi H, Takai M, Yoo S. 23.  et al. 2012. GPR30 regulates the EGFR-Akt cascade and predicts lower survival in patients with ovarian cancer. J. Ovarian Res. 5:35 [Google Scholar]
  24. Huang GS, Gunter MJ, Arend RC, Li M, Arias-Pulido H. 24.  et al. 2009. GPR30 and estrogen receptor β are markers of disease progression in uterine carcinosarcoma. Gynecol. Oncol. 112:S74–75 [Google Scholar]
  25. Huang S, Zhang A, Ding G, Chen R. 25.  2009. Aldosterone-induced mesangial cell proliferation is mediated by EGF receptor transactivation. Am. J. Physiol. Renal. Physiol. 296:F1323–33 [Google Scholar]
  26. McEneaney V, Dooley R, Yusef YR, Keating N, Quinn U. 26.  et al. 2010. Protein kinase D1 modulates aldosterone-induced ENaC activity in a renal cortical collecting duct cell line. Mol. Cell Endocrinol. 325:8–17 [Google Scholar]
  27. Liu SL, Schmuck S, Chorazcyzewski JZ, Gros R, Feldman RD. 27.  2003. Aldosterone regulates vascular reactivity: short-term effects mediated by phosphatidylinositol 3-kinase–dependent nitric oxide synthase activation. Circulation 108:2400–6 [Google Scholar]
  28. Filardo EJ, Quinn JA, Bland KI, Frackelton AR Jr.. 28.  2000. Estrogen-induced activation of Erk-1 and Erk-2 requires the G protein-coupled receptor homolog, GPR30, and occurs via trans-activation of the epidermal growth factor receptor through release of HB-EGF. Mol. Endocrinol. 14:1649–60 [Google Scholar]
  29. Thomas P, Pang Y, Filardo EJ, Dong J. 29.  2005. Identity of an estrogen membrane receptor coupled to a G protein in human breast cancer cells. Endocrinology 146:624–32 [Google Scholar]
  30. Cheng SB, Quinn JA, Graeber CT, Filardo EJ. 30.  2011. Down-modulation of the G-protein-coupled estrogen receptor, GPER, from the cell surface occurs via a trans-Golgi-proteasome pathway. J. Biol. Chem. 286:22441–55 [Google Scholar]
  31. Sandén C, Broselid S, Cornmark L, Andersson K, Daszkiewicz-Nilsson J. 31.  et al. 2011. G protein-coupled estrogen receptor 1/G protein-coupled receptor 30 localizes in the plasma membrane and traffics intracellularly on cytokeratin intermediate filaments. Mol. Pharmacol. 79:400–10 [Google Scholar]
  32. Chan QKY, Lam HM, Ng CF, Lee AYY, Chan ESY. 32.  et al. 2010. Activation of GPR30 inhibits the growth of prostate cancer cells through sustained activation of Erk1/2, c-jun/c-fos-dependent upregulation of p21, and induction of G2 cell-cycle arrest. Cell Death Differ. 17:1511–23 [Google Scholar]
  33. Ylikomi T, Vienonen A, Ahola TM. 33.  2004. G protein-coupled receptor 30 down-regulates cofactor expression and interferes with the transcriptional activity of glucocorticoid. Eur. J. Biochem. 271:4159–68 [Google Scholar]
  34. Lin BC, Suzawa M, Blind RD, Tobias SC, Bulun SE. 34.  et al. 2009. Stimulating the GPR30 estrogen receptor with a novel tamoxifen analogue activates SF-1 and promotes endometrial cell proliferation. Cancer Res. 69:5415–23 [Google Scholar]
  35. Zhou X, Wang S, Wang Z, Feng X, Liu P. 35.  et al. 2015. Estrogen regulates Hippo signaling via GPER in breast cancer. J. Clin. Investig. 125:2123–35 [Google Scholar]
  36. Kanda N, Watanabe S. 36.  2004. 17β-estradiol stimulates the growth of human keratinocytes by inducing cyclin D2 expression. J. Investig. Dermatol. 123:319–28 [Google Scholar]
  37. Kanda N, Watanabe S. 37.  2003. 17β-estradiol inhibits oxidative stress-induced apoptosis in keratinocytes by promoting Bcl-2 expression. J. Investig. Dermatol. 121:1500–9 [Google Scholar]
  38. Kent RS. Lean A, Lefkowitz RJ. 38. , De 1980. A quantitative analysis of beta-adrenergic receptor interactions: resolution of high and low affinity states of the receptor by computer modeling of ligand binding data. Mol. Pharmacol. 17:14–23 [Google Scholar]
  39. Motulsky HJ, Insel PA. 39.  1982. Adrenergic receptors in man: direct identification, physiologic regulation, and clinical alterations. N. Engl. J. Med. 307:18–29 [Google Scholar]
  40. Prossnitz ER, Arterburn JB. 40.  2015. International Union of Basic and Clinical Pharmacology. XCVII. G protein-coupled estrogen receptor and its pharmacologic modulators. Pharmacol. Rev. 67:505–40 [Google Scholar]
  41. Feldman RD, Limbird LE. 41.  2015. Copernicus revisited: overturning Ptolemy's view of the GPER universe. Trends Endocrinol. Metab. 26:592–94 [Google Scholar]
  42. Rigiracciolo DC, Scarpelli A, Lappano R, Pisano A, Santolla MF. 42.  et al. 2016. GPER is involved in the stimulatory effects of aldosterone in breast cancer cells and breast tumor-derived endothelial cells. Oncotarget 7:94–111 [Google Scholar]
  43. Cheng SB, Dong J, Pang Y, LaRocca J, Hixon M. 43.  et al. 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. Mol. Cell Endocrinol. 382:950–59 [Google Scholar]
  44. Santolla MF. Francesco EM, Lappano R, Rosano C, Abonante S, Maggiolini M. 44. , De 2014. Niacin activates the G protein estrogen receptor (GPER)-mediated signalling. Cell Signal 26:1466–75 [Google Scholar]
  45. Huff MO, Todd SL, Smith AL, Elpers JT, Smith AP. 45.  et al. 2016. Arsenite and cadmium activate MAPK/ERK via membrane estrogen receptors and G-protein coupled estrogen receptor signaling in human lung adenocarcinoma cells. Toxicol. Sci. 152:62–71 [Google Scholar]
  46. Noel SD, Keen KL, Baumann DI, Filardo EJ, Terasawa E. 46.  2009. Involvement of G protein-coupled receptor 30 (GPR30) in rapid action of estrogen in primate LHRH neurons. Mol. Endocrinol. 23:349–59 [Google Scholar]
  47. Sharma G, Prossnitz ER. 47.  2011. Mechanisms of estradiol-induced insulin secretion by the G protein-coupled estrogen receptor GPR30/GPER in pancreatic β-cells. Endocrinology 152:3030–39 [Google Scholar]
  48. Brunsing RL, Prossnitz ER. 48.  2011. Induction of interleukin-10 in the T helper type 17 effector population by the G protein coupled estrogen receptor (GPER) agonist G-1. Immunology 134:93–106 [Google Scholar]
  49. Dennis MK, Burai R, Ramesh C, Petrie WK, Alcon SN. 49.  et al. 2009. In vivo effects of a GPR30 antagonist. Nat. Chem. Biol. 5:421–27 [Google Scholar]
  50. Otto C, Fuchs I, Kauselmann G, Kern H, Zevnik B. 50.  et al. 2009. GPR30 does not mediate estrogenic responses in reproductive organs in mice. Biol. Reprod. 80:34–41 [Google Scholar]
  51. Barton M, Prossnitz ER. 51.  2015. Emerging roles of GPER in diabetes and atherosclerosis. Trends Endocrinol. Metab. 26:185–92 [Google Scholar]
  52. Langer G, Bader B, Meoli L, Isensee J, Delbeck M. 52.  et al. 2010. A critical review of fundamental controversies in the field of GPR30 research. Steroids 75:603–10 [Google Scholar]
  53. Haas E, Bhattacharya I, Brailoiu E, Damjanović M, Brailoiu GC. 53.  et al. 2009. Regulatory role of G protein–coupled estrogen receptor for vascular function and obesity. Circ. Res. 104:288–91 [Google Scholar]
  54. Kvingedal AM, Smeland EB. 54.  1997. A novel putative G-protein-coupled receptor expressed in lung, heart and lymphoid tissue. FEBS Lett. 407:59–62 [Google Scholar]
  55. Lindsey SH, Carver KA, Prossnitz ER, Chappell MC. 55.  2011. Vasodilation in response to the GPR30 agonist G-1 is not different from estradiol in the mRen2.Lewis female rat. J. Cardiovasc. Pharmacol. 57:598–603 [Google Scholar]
  56. Li ZL, Liu JC, Liu SB, Li XQ, Yi DH, Zhao MG. 56.  2012. Improvement of vascular function by acute and chronic treatment with the GPR30 agonist G1 in experimental diabetes mellitus. PLOS ONE 7:e38787 [Google Scholar]
  57. Jang EJ, Seok YM, Arterburn JB, Olatunji LA, Kim IK. 57.  2013. GPER-1 agonist G1 induces vasorelaxation through activation of epidermal growth factor receptor-dependent signalling pathway. J. Pharm. Pharmacol. 65:1488–99 [Google Scholar]
  58. Lindsey SH, Liu L, Chappell MC. 58.  2014. Vasodilation by GPER in mesenteric arteries involves both endothelial nitric oxide and smooth muscle cAMP signaling. Steroids 81:99–102 [Google Scholar]
  59. Yu X, Ma H, Barman SA, Sellers M, Stallone JN. 59.  et al. 2011. Activation of G protein-coupled estrogen receptor (GPER) induces endothelium-independent relaxation of coronary artery smooth muscle. Am. J. Physiol. Endocrinol. Metab. 301:E882–88 [Google Scholar]
  60. Arefin S, Simoncini T, Wieland R, Hammarqvist F, Spina S. 60.  et al. 2014. Vasodilatory effects of the selective GPER agonist G-1 is maximal in arteries of postmenopausal women. Maturitas 78:123–30 [Google Scholar]
  61. Lindsey SH, Cohen JA, Brosnihan KB, Gallagher PE, Chappell MC. 61.  2009. Chronic treatment with the G protein-coupled receptor 30 agonist G-1 decreases blood pressure in ovariectomized mRen2. Lewis rats. Endocrinology 150:3753–58 [Google Scholar]
  62. Martensson UE, Salehi SA, Windahl S, Gomez MF, Sward K. 62.  et al. 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 150:687–98 [Google Scholar]
  63. Feldman RD, Gros R, Ding Q, Hussain Y, Ban MR. 63.  et al. 2014. A common hypofunctional genetic variant of GPER is associated with increased blood pressure in women. Br. J. Clin. Pharmacol. 78:1441–52 [Google Scholar]
  64. Giess M, Lattrich C, Springwald A, Goerse R, Ortmann O, Treeck O. 64.  2010. GPR30 gene polymorphisms are associated with progesterone receptor status and histopathological characteristics of breast cancer patients. J. Steroid Biochem. Mol. Biol. 118:7–12 [Google Scholar]
  65. Meyer MR, Fredette NC, Howard TA, Hu C, Ramesh C. 65.  et al. 2015. G protein-coupled estrogen receptor protects from atherosclerosis. Sci. Rep. 4:7564 [Google Scholar]
  66. Hussain Y, Ding Q, Connelly PW, Brunt JH, Ban MR. 66.  et al. 2015. G-protein estrogen receptor as a regulator of low-density lipoprotein cholesterol metabolism: cellular and population genetic studies. Arterioscler. Thromb. Vasc. Biol. 35:213–21 [Google Scholar]
  67. Weil BR, Manukyan MC, Herrmann JL, Wang Y, Abarbanell AM. 67.  et al. 2010. Signaling via GPR30 protects the myocardium from ischemia/reperfusion injury. Surgery 148:436–43 [Google Scholar]
  68. Deschamps AM, Murphy E. 68.  2009. Activation of a novel estrogen receptor, GPER, is cardioprotective in male and female rats. Am. J. Physiol. Heart Circ. Physiol. 297:H1806–13 [Google Scholar]
  69. Broughton BR, Brait VH, Kim HA, Lee S, Chu HX. 69.  et al. 2014. Sex-dependent effects of G protein-coupled estrogen receptor activity on outcome after ischemic stroke. Stroke 45:835–41 [Google Scholar]
  70. Holm A, Baldetorp B, Olde B, Leeb-Lundberg LM, Nilsson BO. 70.  2011. The GPER1 agonist G-1 attenuates endothelial cell proliferation by inhibiting DNA synthesis and accumulating cells in the S and G2 phases of the cell cycle. J. Vasc. Res. 48:327–35 [Google Scholar]
  71. Li F, Yu X, Szynkarski CK, Meng C, Zhou B. 71.  et al. 2013. Activation of GPER induces differentiation and inhibition of coronary artery smooth muscle cell proliferation. PLOS ONE 8:e64771 [Google Scholar]
  72. Wang H, Zhao Z, Lin M, Groban L. 72.  2015. Activation of GPR30 inhibits cardiac fibroblast proliferation. Mol. Cell Biochem. 405:135–48 [Google Scholar]
  73. Pandey DP, Lappano R, Albanito L, Madeo A, Maggiolini M, Picard D. 73.  2009. Estrogenic GPR30 signalling induces proliferation and migration of breast cancer cells through CTGF. EMBO J 28:523–32 [Google Scholar]
  74. Luo H, Yang G, Yu T, Luo S, Wu C. 74.  et al. 2014. GPER-mediated proliferation and estradiol production in breast cancer-associated fibroblasts. Endocr. Relat. Cancer 21:355–69 [Google Scholar]
  75. Vivacqua A, Bonofiglio D, Albanito L, Madeo A, Rago V. 75.  et al. 2006. 17β-estradiol, genistein, and 4-hydroxytamoxifen induce the proliferation of thyroid cancer cells through the G protein-coupled receptor GPR30. Mol. Pharmacol. 70:1414–23 [Google Scholar]
  76. Albanito L, Madeo A, Lappano R, Vivacqua A, Rago V. 76.  et al. 2007. G protein–coupled receptor 30 (GPR30) mediates gene expression changes and growth response to 17β-estradiol and selective GPR30 ligand G-1 in ovarian cancer cells. Cancer Res 67:1859–66 [Google Scholar]
  77. Noda-Seino H, Sawada K, Hayakawa J, Ohyagi-Hara C, Mabuchi S. 77.  et al. 2013. Estradiol and raloxifene induce the proliferation of osteoblasts through G-protein-coupled receptor GPR30. J. Endocrinol. Investig. 36:21–27 [Google Scholar]
  78. He YY, Cai B, Yang YX, Liu XL, Wan XP. 78.  2009. Estrogenic G protein-coupled receptor 30 signaling is involved in regulation of endometrial carcinoma by promoting proliferation, invasion potential, and interleukin-6 secretion via the MEK/ERK mitogen-activated protein kinase pathway. Cancer Sci 100:1051–61 [Google Scholar]
  79. Jacenik D, Cygankiewicz AI, Krajewska WM. 79.  2016. The G protein-coupled estrogen receptor as a modulator of neoplastic transformation. Mol. Cell. Endocrinol. 429:10–18 [Google Scholar]
  80. Balhuizen A, Kumar R, Amisten S, Lundquist I, Salehi A. 80.  2010. Activation of G protein-coupled receptor 30 modulates hormone secretion and counteracts cytokine-induced apoptosis in pancreatic islets of female mice. Mol. Cell Endocrinol. 320:16–24 [Google Scholar]
  81. Ahola TM, Manninen T, Alkio N, Ylikomi T. 81.  2002. G protein-coupled receptor 30 is critical for a progestin-induced growth inhibition in MCF-7 breast cancer cells. Endocrinology 143:3376–84 [Google Scholar]
  82. Ariazi EA, Brailoiu E, Yerrum S, Shupp HA, Slifker MJ. 82.  et al. 2010. The G protein–coupled receptor GPR30 inhibits proliferation of estrogen receptor–positive breast cancer cells. Cancer Res 70:1184–94 [Google Scholar]
  83. Chimento A, Casaburi I, Bartucci M, Patrizii M, Dattilo R. 83.  et al. 2013. Selective GPER activation decreases proliferation and activates apoptosis in tumor Leydig cells. Cell Death Dis 4:e747 [Google Scholar]
  84. Wang C, Lv X, Jiang C, Davis JS. 84.  2012. The putative G-protein coupled estrogen receptor agonist G-1 suppresses proliferation of ovarian and breast cancer cells in a GPER-independent manner. Am. J. Transl. Res. 4:390–402 [Google Scholar]
  85. Gros R, Hussain Y, Chorazyczewski J, Pickering G, Feldman RD. 85.  2016. Extent of vascular remodeling is dependent on the balance between estrogen receptor α and G-protein–coupled estrogen receptor. Hypertension 681225–35
  86. Pupo M, Pisano A, Abonante S, Maggiolini M, Musti AM. 86.  2014. GPER activates Notch signaling in breast cancer cells and cancer-associated fibroblasts (CAFs). Int. J. Biochem. Cell Biol. 46:56–67 [Google Scholar]
  87. Tsai CL, Wu HM, Lin CY, Lin YJ, Chao A. 87.  et al. 2013. Estradiol and tamoxifen induce cell migration through GPR30 and activation of focal adhesion kinase (FAK) in endometrial cancers with low or without nuclear estrogen receptor α (ERα). PLOS ONE 8e72999
  88. Feldman RD, Ding Q, Hussain Y, Limbird LE, Pickering JG, Gros R. 88.  2016. Aldosterone mediates metastatic spread of renal cancer via the G protein–coupled estrogen receptor (GPER). FASEB J. 30:2086–96 [Google Scholar]
  89. De Marco P, Lappano R, Francesco EM, Cirillo F, Pupo M. 89.  et al. 2016. GPER signalling in both cancer-associated fibroblasts and breast cancer cells mediates a feedforward IL1β/IL1R1 response. Sci. Rep. 6:24354 [Google Scholar]
  90. Heerkens EHJ, Quinn L, Withers SB, Heagerty AM. 90.  2014. β Integrins mediate FAK Y397 autophosphorylation of resistance arteries during eutrophic inward remodeling in hypertension. J. Vasc. Res. 51:305–14 [Google Scholar]
  91. Faxon DP, Coats W, Currier J. 91.  1997. Remodeling of the coronary artery after vascular injury. Prog. Cardiovasc. Dis. 40:129–40 [Google Scholar]
  92. Intengan HD, Schiffrin EL. 92.  2001. Vascular remodeling in hypertension: roles of apoptosis, inflammation, and fibrosis. Hypertension 38:581–87 [Google Scholar]
  93. Goel SA, Guo LW, Liu B, Kent KC. 93.  2012. Mechanisms of post-intervention arterial remodelling. Cardiovasc. Res. 96:363–71 [Google Scholar]
  94. Chakrabarti S, Davidge ST. 94.  2016. Analysis of G-protein coupled receptor 30 (GPR30) on endothelial inflammation. Methods Mol. Biol. 1366:503–16 [Google Scholar]
  95. Liu L, Kashyap S, Murphy B, Hutson DD, Budish RA. 95.  et al. 2016. GPER activation ameliorates aortic remodeling induced by salt-sensitive hypertension. Am. J. Physiol. Heart Circ. Physiol. 30:H953–61 [Google Scholar]
  96. Lindsey SH, da Silva AS, Silva MS, Chappell MC. 96.  2013. Reduced vasorelaxation to estradiol and G-1 in aged female and adult male rats is associated with GPR30 downregulation. Am. J. Physiol. Endocrinol. Metab. 305:E113–18 [Google Scholar]
  97. Jessup JA, Lindsey SH, Wang H, Chappell MC, Groban L. 97.  2010. Attenuation of salt-induced cardiac remodeling and diastolic dysfunction by the GPER agonist G-1 in female mRen2.Lewis rats. PLOS ONE 5:e15433 [Google Scholar]
  98. Kang S, Liu Y, Sun D, Zhou C, Liu A. 98.  et al. 2012. Chronic activation of the G protein-coupled receptor 30 with agonist G-1 attenuates heart failure. PLOS ONE 7:e48185 [Google Scholar]
  99. Zhao Z, Wang H, Jessup JA, Lindsey SH, Chappell MC, Groban L. 99.  2014. Role of estrogen in diastolic dysfunction. Am. J. Physiol. Heart Circ. Physiol. 306:H628–40 [Google Scholar]
  100. Chimento A, Sirianni R, Casaburi I, Zolea F, Rizza P. 100.  et al. 2015. GPER agonist G-1 decreases adrenocortical carcinoma (ACC) cell growth in vitro and in vivo. Oncotarget 6:19190–203 [Google Scholar]
  101. Wei W, Chen ZJ, Zhang KS, Yang XL, Wu YM. 101.  et al. 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 Dis 5:e1428 [Google Scholar]

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error