ArticleThe Journal of steroid biochemistry and molecular biology2018
Role of GPER in estrogen-dependent nitric oxide formation and vasodilation.
Article in The Journal of steroid biochemistry and molecular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 119 citations in OpenAlex.
- Aging is associated with altered estrogen receptor expression and alters redox protein balance in human female skeletal muscle.GeroScience · 2026Article
- Activation of the G-protein coupled estrogen receptor 1 (GPER1) reduces transient receptor potential vanilloid 1 (TRPV1) activity and human iPSC-derived nociceptive neuron firing.Stem cell research & therapy · 2026Article
- Sex differences in cardiovascular‑kidney‑metabolic syndrome: From pathogenesis to treatment response (Review).International journal of molecular medicine · 2026Review
- Menopause and vascular endothelial health: Is it all about the oestrogen?Experimental physiology · 2026Review
- Sex-specific insights in atherosclerosis and pulmonary arterial hypertension: an overlooked comorbidity.Frontiers in cardiovascular medicine · 2026Review
- The multifaceted impact of a high-salt environment on the immune system and its contribution to salt-sensitive hypertension.Biochemistry and biophysics reports · 2025Review
- Mineralocorticoid and estrogen receptors as sex-dependent modulators of vascular health in aging and obesity.The Journal of pharmacology and experimental therapeutics · 2025Review
- The role of estrogen in the sex difference for the risk factors of heart failure with preserved ejection fraction.Biology direct · 2025Review
- Article
- Higher amounts of habitual physical activity changes the relationship between hot flashes and subclinical cardiovascular disease risk.Physiological reports · 2025Article
- Short-term estradiol administration does not restore endothelin-B receptor-mediated vasodilation in postmenopausal women.American journal of physiology. Heart and circulatory physiology · 2025Article
- Promotion of nitric oxide production: mechanisms, strategies, and possibilities.Frontiers in physiology · 2025Review
- Contemporary menopausal hormone therapy and risk of cardiovascular disease: Swedish nationwide register based emulated target trial.BMJ (Clinical research ed.) · 2024Article
- The Estrogen-Autophagy Axis: Insights into Cytoprotection and Therapeutic Potential in Cancer and Infection.International journal of molecular sciences · 2024Review
- GPER expression prevents estrogen-induced urinary retention in obese mice.The Journal of steroid biochemistry and molecular biology · 2024Article
- GPER deficiency impedes murine myocutaneous revascularization and wound healing.Scientific reports · 2024Article
- The Role of Catestatin in Preeclampsia.International journal of molecular sciences · 2024Review
- Hallmarks of aging: middle-aging hypovascularity, tissue perfusion and nitric oxide perspective on healthspan.Frontiers in aging · 2024Article
- Sex differences in blood pressure regulation and hypertension: renal, hemodynamic, and hormonal mechanisms.Physiological reviews · 2024Review
- GPER: An Estrogen Receptor Key in Metastasis and Tumoral Microenvironments.International journal of molecular sciences · 2023Review
9 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Estrogens are potent regulators of vasomotor tone, yet underlying receptor- and ligand-specific signaling pathways remain poorly characterized. The primary physiological estrogen 17β-estradiol (E2), a non-selective agonist of classical nuclear estrogen receptors (ERα and ERβ) as well as the G protein-coupled estrogen receptor (GPER), stimulates formation of the vasodilator nitric oxide (NO) in endothelial cells. Here, we studied the contribution of GPER signaling in E2-dependent activation of endothelial NO formation and subsequent vasodilation. Employing E2 and the GPER-selective agonist G-1, we investigated eNOS phosphorylation and NO formation in human endothelial cells, and endothelium-dependent vasodilation in the aortae of wild-type and Gper-deficient mice. Both E2 and G-1 induced phosphorylation of eNOS at the activation site Ser1177 to similar extents. Endothelial NO production to E2 was comparable to that of G-1, and was substantially reduced after pharmacological inhibition of GPER. Similarly, the clinically used ER-targeting drugs 4OH-tamoxifen, raloxifene, and ICI182,780 (faslodex, fulvestrant™) induced NO formation in part via GPER. We identified c-Src, EGFR, PI3K and ERK signaling pathways to be involved in GPER-dependent NO formation. In line with activation of NO formation in cells, E2 and G-1 induced equally potent vasodilation in the aorta of wild-type mice. Gper deletion completely abrogated the vasodilator response to G-1, while reducing the response to E2 by ∼50%. These findings indicate that a substantial portion of E2-induced endothelium-dependent vasodilation and NO formation is mediated by GPER. Thus, selective targeting of vascular GPER may be a suitable approach to activate the endothelial NO pathway, possibly leading to reduced vasomotor tone and inhibition of atherosclerotic vascular disease.
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