Abstract 113: Female Protection From Arterial Stiffness Diminishes With G Protein-Coupled Estrogen Receptor Deletion or Angiotensin II Hypertension

Hypertension ◽  
2018 ◽  
Vol 72 (Suppl_1) ◽  
Author(s):  
Benard O Ogola ◽  
Caleb M Abshire ◽  
Gabrielle L Clark ◽  
Dylan J Lawrence ◽  
Margaret A Zimmerman ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Angiotensin Ii ◽  
Arterial Stiffness ◽  
G Protein ◽  
G Protein Coupled

scholarly journals G Protein-Coupled Estrogen Receptor Protects From Angiotensin II-Induced Increases in Pulse Pressure and Oxidative Stress

2019 ◽  
Vol 10 ◽  
Author(s):  
Benard O. Ogola ◽  
Margaret A. Zimmerman ◽  
Venkata N. Sure ◽  
Kaylee M. Gentry ◽  
Jennifer L. Duong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Estrogen Receptor ◽  
Angiotensin Ii ◽  
G Protein ◽  
Pulse Pressure ◽  
G Protein Coupled ◽  
And Oxidative Stress

Abstract P170: Similarities And Differences In The Vascular Impact Of Estrogen Loss Versus G Protein-coupled Estrogen Receptor Deletion

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Isabella M Kilanowski-Doroh ◽  
Tristen J Wong ◽  
Benard O Ogola ◽  
Nicholas Harris ◽  
Alec Horton ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Estrogen Receptor ◽  
Smooth Muscle ◽  
Arterial Stiffness ◽  
G Protein ◽  
Vascular Stiffness ◽  
Area Fraction ◽  
Increased Risk ◽  
The Impact ◽  
G Protein Coupled

Women in their postmenopausal years have an increased risk of cardiovascular disease, and recent research suggests that increased vascular stiffness can be detected within a year of the onset of menopause. We have previously demonstrated that the G Protein-Coupled Estrogen Receptor (GPER) protects the vasculature without noticeable changes in blood pressure, but little is known about the underlying structural changes that provide protection. In this study we assessed the impact of estrogen and the G protein-coupled estrogen receptor (GPER) on vascular health, with the hypothesis that loss of estrogen or deletion of smooth muscle cell (smc)-GPER would similarly increase vascular stiffness. Female mice were separated into three cohorts: intact wildtype, ovariectomized (OVX), and GPER smc-KO. OVX occurred at 8 weeks of age and 8 weeks later blood pressure was measured via tail-cuff plethysmography, arterial stiffness was measured as pulse wave velocity (PWV) via high resolution ultrasound, and carotids were excised for biaxial pressure myography and imaging. Uterine weight in OVX mice (0.03 g) was significantly lower than intact mice (0.1 g; p=0.0002) confirming the loss of estrogen. No difference was observed in systolic blood pressure, however, both the OVX (1.5 m/s) and smc-KO (1.9 m/s) groups had significantly higher PWV than intact controls (1.2 m/s; p=0.02 and p=0.03, respectively). Carotids of OVX (366 μm) and smc-KO (389 μm) mice had a smaller outer diameter versus controls (441 μm; p >0.05) without a difference in thickness. Despite the similar responses of OVX and smc-KO groups, Masson’s trichrome staining of carotid sections showed significantly more smooth muscle area fraction in OVX (p=0.005), but not KO mice, and no difference in collagen area fraction. These data indicate that while estrogen loss and smc-KO of GPER both increase arterial stiffness, increased smooth muscle due to estrogen loss is likely not modulated through GPER. Future experiments will aim to understand how other components, such as extracellular matrix genes, may be affected by loss of GPER.

scholarly journals G Protein-Coupled Estrogen Receptor 1 (GPER) as a Novel Target for Schizophrenia Drug Treatment

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Danielle S Macêdo ◽  
Lia Lira Olivier Sanders ◽  
Raimunda das Candeias ◽  
Cyntia de Freitas Montenegro ◽  
David Freitas de Lucena ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptors ◽  
G Protein ◽  
Brain Inflammation ◽  
Antipsychotic Treatment ◽  
New Class ◽  
Estrogen Receptor Modulators ◽  
Novel Target ◽  
G Protein Coupled ◽  
Estrogen Receptor 1

Abstract The observation that a person’s sex influences the onset age of schizophrenia, the course of the disease, and antipsychotic treatment response suggests a possible role for estrogen receptors in the pathophysiology of schizophrenia. Indeed, treatment with adjunctive estrogen or selective estrogen receptor modulators (SERMs) are known to reduce schizophrenia symptoms. While estrogen receptors (ER)α and ERβ have been studied, a third and more recently discovered estrogen receptor, the G protein-coupled estrogen receptor 1 (GPER), has been largely neglected. GPER is a membrane receptor that regulates non-genomic estrogen functions, such as the modulation of emotion and inflammatory response. This review discusses the possible role of GPER in brain impairments seen in schizophrenia and in its potential as a therapeutic target. We conducted a comprehensive literature search in the PubMed/MEDLINE database, using the following search terms: “Schizophrenia,” “Psychosis,” “GPER1 protein,” “Estrogen receptors,” “SERMS,” “GPER1 agonism, “Behavioral symptoms,” “Brain Inflammation.” Studies involving GPER in schizophrenia, whether preclinical or human studies, have been scarce, but the results are encouraging. Agonism of the GPER receptor could prove to be an essential mechanism of action for a new class of “anti-schizophrenia” drugs.

scholarly journals G Protein-Coupled Estrogen Receptor in Cancer and Stromal Cells: Functions and Novel Therapeutic Perspectives

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 672
Author(s):  
Richard A. Pepermans ◽  
Geetanjali Sharma ◽  
Eric R. Prossnitz
Keyword(s):  
Estrogen Receptor ◽  
G Protein ◽  
Inflammatory Diseases ◽  
Therapy Resistance ◽  
Breast Cancers ◽  
Obesity And Diabetes ◽  
Therapeutic Value ◽  
Health And Disease ◽  
Multiple Cells ◽  
G Protein Coupled

Estrogen is involved in numerous physiological and pathophysiological systems. Its role in driving estrogen receptor-expressing breast cancers is well established, but it also has important roles in a number of other cancers, acting both on tumor cells directly as well as in the function of multiple cells of the tumor microenvironment, including fibroblasts, immune cells, and adipocytes, which can greatly impact carcinogenesis. One of its receptors, the G protein-coupled estrogen receptor (GPER), has gained much interest over the last decade in both health and disease. Increasing evidence shows that GPER contributes to clinically observed endocrine therapy resistance in breast cancer while also playing a complex role in a number of other cancers. Recent discoveries regarding the targeting of GPER in combination with immune checkpoint inhibition, particularly in melanoma, have led to the initiation of the first Phase I clinical trial for the GPER-selective agonist G-1. Furthermore, its functions in metabolism and corresponding pathophysiological states, such as obesity and diabetes, are becoming more evident and suggest additional therapeutic value in targeting GPER for both cancer and other diseases. Here, we highlight the roles of GPER in several cancers, as well as in metabolism and immune regulation, and discuss the therapeutic value of targeting this estrogen receptor as a potential treatment for cancer as well as contributing metabolic and inflammatory diseases and conditions.

Sign in / Sign up

Export Citation Format

Share Document