G Protein-coupled Estrogen Receptor 1 As a Novel Regulator of Blood Pressure

Overview

Journal Am J Physiol Renal Physiol

Publisher American Physiological Society

Specialties Nephrology
Physiology

Date 2020 Sep 7

PMID 32893662

Citations 14

Authors

Eman Y Gohar

Affiliations

Soon will be listed here.

Abstract

The mechanisms underlying hypertension are multifaceted and incompletely understood. New evidence suggests that G protein-coupled estrogen receptor 1 (GPER1) mediates protective actions within the cardiovascular and renal systems. This mini-review focuses on recent advancements in our understanding of the vascular, renal, and cardiac GPER1-mediated mechanisms that influence blood pressure regulation. We emphasize clinical and basic evidence that suggests GPER1 as a novel target to aid therapeutic strategies for hypertension. Furthermore, we discuss current controversies and challenges facing GPER1-related research.

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References

Arefin S, Simoncini T, Wieland R, Hammarqvist F, Spina S, Goglia L . Vasodilatory effects of the selective GPER agonist G-1 is maximal in arteries of postmenopausal women. Maturitas. 2014; 78(2):123-30. DOI: 10.1016/j.maturitas.2014.04.002. View

Camilletti M, Abeledo-Machado A, Ferraris J, Perez P, Faraoni E, Pisera D . Role of GPER in the anterior pituitary gland focusing on lactotroph function. J Endocrinol. 2018; 240(2):99-110. DOI: 10.1530/JOE-18-0402. View

Meyer M, Fredette N, Barton M, Prossnitz E . Regulation of vascular smooth muscle tone by adipose-derived contracting factor. PLoS One. 2013; 8(11):e79245. PMC: 3823600. DOI: 10.1371/journal.pone.0079245. View

Wang H, Jessup J, Lin M, Chagas C, Lindsey S, Groban L . Activation of GPR30 attenuates diastolic dysfunction and left ventricle remodelling in oophorectomized mRen2.Lewis rats. Cardiovasc Res. 2012; 94(1):96-104. PMC: 3307382. DOI: 10.1093/cvr/cvs090. View

Lindsey S, Carver K, Prossnitz E, Chappell M . Vasodilation in response to the GPR30 agonist G-1 is not different from estradiol in the mRen2.Lewis female rat. J Cardiovasc Pharmacol. 2011; 57(5):598-603. PMC: 3095760. DOI: 10.1097/FJC.0b013e3182135f1c. View

Meyer M, Haas E, Barton M . Gender differences of cardiovascular disease: new perspectives for estrogen receptor signaling. Hypertension. 2006; 47(6):1019-26. DOI: 10.1161/01.HYP.0000223064.62762.0b. View

Spary E, Chapman S, Sinfield J, Maqbool A, Kaye J, Batten T . Novel G protein-coupled oestrogen receptor GPR30 shows changes in mRNA expression in the rat brain over the oestrous cycle. Neurosignals. 2012; 21(1-2):14-27. DOI: 10.1159/000333296. View

Wang H, Sun X, Lin M, Ferrario C, Van Remmen H, Groban L . G protein-coupled estrogen receptor (GPER) deficiency induces cardiac remodeling through oxidative stress. Transl Res. 2018; 199:39-51. PMC: 6151279. DOI: 10.1016/j.trsl.2018.04.005. View

Liu S, Ding T, Liu H, Jian L . GPER was Associated with Hypertension in Post-Menopausal Women. Open Med (Wars). 2018; 13:338-343. PMC: 6110139. DOI: 10.1515/med-2018-0051. View

10.

Meyer M, Amann K, Field A, Hu C, Hathaway H, Kanagy N . Deletion of G protein-coupled estrogen receptor increases endothelial vasoconstriction. Hypertension. 2011; 59(2):507-12. PMC: 3266468. DOI: 10.1161/HYPERTENSIONAHA.111.184606. View

11.

Maggiolini M, Vivacqua A, Fasanella G, Grazia Recchia A, Sisci D, Pezzi V . The G protein-coupled receptor GPR30 mediates c-fos up-regulation by 17beta-estradiol and phytoestrogens in breast cancer cells. J Biol Chem. 2004; 279(26):27008-16. DOI: 10.1074/jbc.M403588200. View

12.

Alencar A, da Silva J, Lin M, Silva A, Sun X, Ferrario C . Effect of Age, Estrogen Status, and Late-Life GPER Activation on Cardiac Structure and Function in the Fischer344×Brown Norway Female Rat. J Gerontol A Biol Sci Med Sci. 2016; 72(2):152-162. PMC: 5233906. DOI: 10.1093/gerona/glw045. View

13.

Zimmerman M, Budish R, Kashyap S, Lindsey S . GPER-novel membrane oestrogen receptor. Clin Sci (Lond). 2016; 130(12):1005-16. PMC: 5125080. DOI: 10.1042/CS20160114. View

14.

Ferreira N, Cau S, Silva M, Manzato C, Mestriner F, Matsumoto T . Diabetes impairs the vascular effects of aldosterone mediated by G protein-coupled estrogen receptor activation. Front Pharmacol. 2015; 6:34. PMC: 4345803. DOI: 10.3389/fphar.2015.00034. View

15.

Caroccia B, Seccia T, Piazza M, Prisco S, Zanin S, Iacobone M . Aldosterone Stimulates Its Biosynthesis Via a Novel GPER-Mediated Mechanism. J Clin Endocrinol Metab. 2019; 104(12):6316-6324. DOI: 10.1210/jc.2019-00043. View

16.

Filardo E, Quinn J, Bland K, Frackelton Jr A . 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. 2000; 14(10):1649-60. DOI: 10.1210/mend.14.10.0532. View

17.

Debortoli A, Rouver W, Delgado N, Mengal V, Claudio E, Pernomian L . GPER modulates tone and coronary vascular reactivity in male and female rats. J Mol Endocrinol. 2017; 59(2):171-180. DOI: 10.1530/JME-16-0117. View

18.

Li Y, Ding X, Li H, Zhang Y, Bao J . Role of G protein-coupled estrogen receptor 1 in modulating transforming growth factor-β stimulated mesangial cell extracellular matrix synthesis and migration. Mol Cell Endocrinol. 2014; 391(1-2):50-9. DOI: 10.1016/j.mce.2014.04.014. View

19.

Barton M, Meyer M . Postmenopausal hypertension: mechanisms and therapy. Hypertension. 2009; 54(1):11-8. DOI: 10.1161/HYPERTENSIONAHA.108.120022. View

20.

Liu S, Le May C, Wong W, Ward R, Clegg D, Marcelli M . Importance of extranuclear estrogen receptor-alpha and membrane G protein-coupled estrogen receptor in pancreatic islet survival. Diabetes. 2009; 58(10):2292-302. PMC: 2750222. DOI: 10.2337/db09-0257. View