Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, ChinaChina
Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, ChinaChina
Department of Pediatrics, Women & Infants Hospital, Warren Alpert Medical School of Brown University, Providence, RI, USA Gender has a crucial influence on incidence and prognosis of chronic and acute kid - ney diseases since women generally have a lower morbidity and mortality compared to men.
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Gender has a crucial influence on incidence and prognosis of chronic and acute kidney diseases since women generally have a lower morbidity and mortality compared to men.1,2 Several studies have reported the capability of estrogen to promote homeostatic and protective effects in the kidney via a pregenomic mechanism that is mediated by G protein-coupled receptor 30 (GPR30), but not by classic Estrogen Receptors (ER), ERα or ERβ.2 GPR30 was first cloned as an orphan receptor from a Burkitt’s lymphoma cell line3 and then confirmed in other cell lines.4 Prior studies have demonstrated that GPR30 is a specific, high affinity, Gs -coupled estrogen membrane receptor activated by naturally occurring and synthetic estrogens and antiestrogens including estradiol-17β, G1, tamoxifen, ICI182,780, Genestein and Bisphenol A, but not by cortisol, progesterone or testosterone in both mammals and fish.5-15 Thus, GPR30 was designated G protein-coupled estrogen receptor-1 (GPER-1) by the International Union of Pharmacology in 2007
Keywords: antiestrogens; estrogens; Genestein
Editorial The G Protein-Coupled Estrogen Receptor * *Corresponding author Shibin Cheng, MD, PhD (GPER-1): A Novel Regulator in the Kidney Assistant Professor Department of Pediatrics Women & Infants Hospital 1* 2 3* Warren Alpert Medical School of Zijun Liu , Na Liu and Shibin Cheng Brown University Providence, RI, USA E-mail: shibin_cheng@brown.edu 1Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China * 2 *Co-Corresponding author 2Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Zijun Liu, MD, PhD Shanghai, China Physician-in-Chief 3 Department of Pediatrics, Women & Infants Hospital, Warren Alpert Medical School of Brown Department of General Surgery University, Providence, RI, USA Nanjing First Hospital Nanjing Medical University Nanjing, China E-mail: liuzijundoctor@sina.com Gender has a crucial influence on incidence and prognosis of chronic and acute kid- 1,2 ney diseases since women generally have a lower morbidity and mortality compared to men.1,2 Volume 1 : Issue 1 Several studies have reported the capability of estrogen to promote homeostatic and protective Article Ref. #: 1000NPOJ1e002 effects in the kidney via a pregenomic mechanism that is mediated by G protein-coupled recep- tor 30 (GPR30), but not by classic Estrogen Receptors (ER), ERα or ERβ.2 GPR30 was first Article History cloned as an orphan receptor from a Burkitt’s lymphoma cell line3 and then confirmed in other th 4 Received: April 16th, 2015 cell lines.4 Prior studies have demonstrated that GPR30 is a specific, high affinity, Gs-coupled th Accepted: April 16th, 2015 estrogen membrane receptor activated by naturally occurring and synthetic estrogens and an- th Published: April 17th, 2015 tiestrogens including estradiol-17β, G1, tamoxifen, ICI182,780, Genestein and Bisphenol A, 5-15 but not by cortisol, progesterone or testosterone in both mammals and fish.5-15 Thus, GPR30 was designated G protein-coupled estrogen receptor-1 (GPER-1) by the International Union of Citation 16 Pharmacology in 2007.
Liu Z, Liu N, Cheng S. The G protein- coupled estrogen receptor (GPER- 1): a novel regulator in the kidney. GPER-1 is highly expressed in kidney tissues albeit with differences regarding its Nephrol Open J. 2015; 1(1): e4-e6. subcellular distribution, which may in part be due to differences in methodological approaches doi: 10.17140/NPOJ-1-e002 17-21 in measuring its expression and activity. Recently, Filardo and coworkers evaluated the topographic mapping of GPER-1 expression in renal tubules using dual immunostaining of the receptors and specific markers for distinct tubules in tissue section.22 The results revealed that GPER-1 immunoreactivity is mainly localized in the distal convoluted tubules and the loop of Henle, and to a lower level in the proximal convoluted tubules.22 Interestingly, the subcellular distribution pattern of GPER-1 in these tubules is distinct: GPER-1 in the distal convoluted tu- bules and the loop of Henle mainly resides in the cytoplasm with less GPER-1 in the basolateral plasma membrane, whereas GPER-1 in the proximal convoluted tubules is primarily located in the basolateral membrane.22 Similar pattern for GPER-1 expression has been observed in male rat renal epithelia.19 Intriguingly, subcellular distribution of GPER-1 is modulated dur- ing the estrus cycle. During the secretory phases of the estrus cycle, GPER-1 is upregulated on cortical epithelia and localized to the basolateral surface during proestrus and redistributed intracellularly during estrus. GPER-1 is down-modulated during luteal phases of the estrus cycle with significantly less receptors on the surface of renal epithelia.22 Lindsey and colleagues reported that GPER-1 imunoreactivity is predominantly localized to the apical surface of the Copyright ©2015 Cheng S. This is an open proximal tubule and minimally to the glomerulus but not to the distal tubules in female hyper- access article distributed under the tensive rat.20 Differences in the subcellular distribution pattern and topographic localization of Creative Commons Attribution 4.0 GPER-1 in distinct renal tubules may suggest that GPER-1 plays differential roles in mediating International License (CC BY 4.0), fluid and electrolyte homeostasis, and that pathological conditions such as hypertension may which permits unrestricted use, distribution, and reproduction in influence subcellular translocation of GPER-1 in renal epithelia. any medium, provided the original work is properly cited. Accumulating evidence has shown multiple roles for GPER-1 in the kidney in the context of physiological and pathological conditions. The spe- Endocrinol. Metab. 2005; 16: 362-367. doi: 10.1016/j.
cific GPER-1 agonist, G1,15 estradiol-17β (E2), and ICI 182,780 tem.2005.08.005 (the ER antagonist and GPER-1 agonist)12 have been reported 2+ + to increase acute Ca2+ concentration and H+-ATPase activity in- 6. Filardo EJ, Thomas P. Mini review: G protein-coupled estro- tracellular calcium signals in microdissected renal tubule seg- gen receptor-1, GPER-1: its mechanism of action and role in ments and isolated intercalated cells but not in similar explants female reproductive cancer, renal and vascular physiology. En- and cell cultures isolated from GPER-1-deleted mice, suggest- docrinology. 2012; 153: 2953-2962. doi: 10.1210/en.2012-1061 + 2+ ing a role for GPER-1 in regulating Na+ and Ca2+ reabsorption in renal tubules and subsequently affecting fluid retention.21 Prior 7. Filardo EJ, Quinn JA, Bland KI, Frackelton Jr, AR. Estrogen- studies revealed that G1 and estradiol-17β induce vasodilation in induced activation of Erk-1 and Erk-2 requires the G protein- female mouse, pig and rat and vasoconstriction in male rat.23 A coupled receptor homolog, GPR30, and occurs via trans-activa- recent study demonstrated that GPER-1 exerts beneficial effects tion of the epidermal growth factor receptor through release of on preventing excessive mesangial matrix production and modu- HB-EGF. Mol. Endocrinol. 2000; 14: 1649-1660.
lates mesangial cell migration.2 Chappell and co-workers have shown that GPER-1 colocalizes with megalin in renal proximal 8. Filardo EJ, Quinn JA, Frackelton Jr AR, Bland KI. Estrogen tubules and that G1 ameliorates salt-induced renal injury in fe- action via the G protein-coupled receptor, GPR30: stimulation male mRen2. Lewis mice independently of changes in systolic of adenylyl cyclase and cAMP mediated attenuation of the epi- blood pressure.20 Estrogen has been shown to ameliorateisch- dermal growth factor receptor-to-MAPK signaling axis. Mol.
emic glomerular endothelial hyperpermeability via a GPER-1- Endocrinol. 2002; 16: 70-84.
mediated mechanism.1 9. Filardo EJ, GraeberCT, Quinn JA, et al. Distribution of GPR30, Collectively, while more work is required to elucidate a seven membrane-spanning estrogen receptor, in primary breast the physiological significance of GPER-1 modulation in the kid- cancer and its association with clinicopathologic determinants of ney, current findings strongly suggest that GPER-1 in the kidney tumor progression. Clin. Cancer Res. 2006; 12: 6359-6366. doi: facilitates selective reabsorption of water and electrolytes, medi- 10.1158/1078-0432.CCR-06-0860 ates renal vascular activities and mesangial cell behavior and reduces proteinuria and oxidative stress.
10. Filardo E, Quinn J, Pang Y, et al. Activation of the novel estrogen receptor G protein-coupled receptor 30 GPR30.at the CONFLICTS OF INTEREST: None.
plasma membrane. Endocrinology. 2007; 148: 3236-3245. doi: 10.1210/en.2006-1605