Effect of G Protein Coupled Estrogen Receptor 1 on Angiotensin Ⅱ-induced Hypertrophy of Cultured Neonatal Rat Cardiomyocytes / 中国循环杂志

Objectives: To observe the effect of activated G-protein coupled estrogen receptor 1 (GPER1) on Angiotensin II (AngII)-induced hypertrophy of cultured neonatal rat cardiomyocytes and explore related mechanisms. Methods: Primary cardiomyocytes derived from 2-to 3-day-old neonatal rats were cultured in vitro. Tandem mass tags (TMT) protein mass spectrometry was used to examine protein expressions; relevant bioinformatics analysis was performed to screen the possible regulatory mechanisms. Cardiomyocytes were divided into 6 groups: (1)Blank control group, (2) AngII group, (3)AngII+G1 (GPER1 activator) group, (4)AngII+G1+G15 (GPER1 inhibitor) group, (5)AngII+G1+U0126 (extracellular ERK inhibitor) group and (6)AngII+G1+MK2206 (AKT inhibitor) group (n=3 for each group). Cardiomyocytes GPER1 expressions, mRNA levels of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), protein levels of ERK, AKT with their interactions, autophagy-related proteins LC3II and LC3I were compared among different groups;impact of GPER1 on cardiomyocytes apoptosis was detected by flowcytometry. Results: AngII induced cardiomyocytes hypertrophy and upregulation of ANP and BNP mRNA levels in a dose-dependent manner (P<0.05). GPER1 expression could be detected on cardiomyocytes by Immunofluorescence technique. qRT-PCR results showed that GPER1 was activated by the specific activator G1 and mRNA expressions of ANP and BNP were inhibited in a dose-dependent manner by the specific activator G1 (P<0.05); mRNA levels of ANP and BNP were re-elevated in AngII+G1+G15 group (P<0.05). Western blotting results showed that protein expression of p-ERK and p-AKT was significantly higher in AngII group and AngII+G1 group than in blank control group (P<0.05), significantly reduced in AngII+G1+G15 group compared with AngII+G1 group (P<0.05); decreased expressions of p-ERK, p-AKT and mRNA levels of ANP,BNP were also detected in AngII+G1+MK2206 group (P<0.05). G1 induced protein expression was similar between AngII+G1 group and AngII+G1+U0126 group. Flowcytometry results indicated that cardiomyocytes apoptosis was similar between AngII+G1 group and AngII group (P>0.05). Ratio of LC3II/LC3I was significantly higher and autophagy levels were significantly enhanced in AngII group than in blank control group (P<0.01), these changes could be significantly reversed in AngII +G1 group (P<0.01 vs. AngII). Conclusions: Activation of GPER1 could inhibit neonatal cardiomyocytes hypertrophy, this effect might be related to AKT and ERK signaling pathway and cell autophagy.

Increased Serum G Protein-coupled Estrogen Receptor 1 Levels and Its Diagnostic Value in Drug Naïve Patients with Major Depressive Disorder

OBJECTIVE: The facts that depression is more prevalent in females than in males and females are exposed to depression more commonly during certain hormonal fluctuating periods indicate the role of sex hormones in physiopathology. Estrogen acts over estrogen receptors alpha and beta and recently identified G protein-coupled estrogen receptor 1 (GPER1). The present study aimed, for the first time, to evaluate serum GPER1 levels in drug-naïve major depressive disorder (MDD) patients. METHODS: The study included 56 newly diagnosed drug-naïve MDD patients aged between 18 and 50 years and 42 age- and gender-matched healthy volunteers. Medical history was obtained and physical examinations, laboratory tests, and the Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A) were performed. The serum GPER1 levels were measured. RESULTS: The HAM-D score was significantly higher in the MDD patients than in the controls. The GPER1 level was significantly higher in the MDD patients than in the controls. A positive correlation was found with GPER1 levels and depression scores. The receiver operating characteristic analysis revealed sensitivity, specificity, positive predictive value, and negative predictive value as 82.1%, 90.5%, 92.0%, and 79.2%, respectively, for the presence of depression, when the serum GPER1 value was ≥0.16. CONCLUSION: This study demonstrated significantly higher serum GPER1 levels in the MDD patients than in the controls, a positive correlation was found between GPER1 levels and depression scores and serum GPER1 level was valuable in predicting the presence of depression.

G-protein Coupled Estrogen Receptor 1 Expression in Primary Breast Cancers and Its Correlation with Clinicopathological Variables / 한국유방암학회지

PURPOSE: G-protein coupled estrogen receptor 1 (GPER) probably play important roles in the progression of breast cancer including endocrine therapeutic resistance. We evaluated GPER in primary breast cancers. METHODS: Immunohistochemistry was used to detect GPER in paraffin-embedded tissues of primary breast cancers from 423 patients and GPER expression was correlated with clinicopathological factors. RESULTS: GPER was expressed in 63.8% of specimens, coexpressed with estrogen receptor alpha (ERalpha) in 36.6% of tumors and was positive in 62.5% of the ERalpha-negative tumors. The expression of GPER had no relationship with the status of ERalpha, progesterone receptor and HER2. Although the expression of GPER was significantly inversely related with nodal status (p=0.045), no correlation between GPER expression and other clinicopathological variables (age, menstruation status, tumor size, stage, histologic grade, Nottingham Prognostic Index or pathological type) was found. CONCLUSION: GPER and ERalpha exhibited independent expression pattern of distribution in primary breast cancers. A long-term follow-up and a more definite molecular phenotype for ER are necessary in confirming studies.