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Martin Wehling
Steroid hormones like aldosterone have been conclusively shown to elicit both late genomic and rapid, nongenomically initiated responses. Aldosterone was among the first for which rapid, clinically relevant effects were even shown in humans. Yet, after over 30 years of research, the nature of receptors involved in rapid actions of aldosterone is still unclear. Such effects may be assigned to the classical, intracellular steroid receptors, in this case mineralocorticoid receptors (MR, class IIa action Mannheim classification)...
January 23, 2017: Journal of Steroid Biochemistry and Molecular Biology
Liang Tang, Shui Zheng, Yan Wang, Fang Li, Meihua Bao, Jie Zeng, Ju Xiang, Huaiqing Luo, Jianming Li
Oestrogen receptors are implicated in the pathogenesis of recurrent spontaneous abortion (RSA). Non-genomic oestrogen responses can be mediated by GPER. The prevalence of polymorphisms in GPER1 gene in RSA was assessed in 747 Chinese women from Yunnan province (171 Bai, 258 Chinese Han, 234 Dai, 33 Achang and 51 Jingpo patients). Snapshot technology was used for genotyping the polymorphisms of the GPER1 gene. The rs4265085G was significantly increased in the Dai and Bai groups versus controls (Dai: P < 0...
January 17, 2017: Reproductive Biomedicine Online
Ali Vaziri-Gohar, Yan Zheng, Kevin D Houston
: Tamoxifen is a common adjuvant treatment for ERalpha-positive breast cancer patients, however acquired resistance abrogates the efficacy of this therapeutic approach. We recently demonstrated that G protein-coupled estrogen receptor 1 (GPER1) mediates tamoxifen action in breast cancer cells by inducing insulin-like growth factor binding protein-1 (IGFBP-1) to inhibit IGF-1-dependent signaling. To determine if dysregulation of IGFBP-1 induction is associated with tamoxifen resistance, IGFBP-1 transcription was measured in tamoxifen-resistant MCF-7 cells (TamR) after tamoxifen (Tam) treatment...
January 17, 2017: Molecular Cancer Research: MCR
Ling Zhang, Wenqian Xiong, Na Li, Hengwei Liu, Haitang He, Yu Du, Zhibing Zhang, Yi Liu
OBJECTIVE: To investigate whether G protein-coupled estrogen receptor (GPER, also known as GPR30 and GPER1) stabilizes hypoxia-inducible factor 1α (HIF-1α) in eutopic endometrium (EuEM) of endometriosis. DESIGN: Immunohistochemical analysis and experimental in vitro study. SETTING: University hospital. PATIENT(S): Patients with or without endometriosis. INTERVENTION(S): The EuEM and normal control endometrium (CoEM) were obtained by curettage...
February 2017: Fertility and Sterility
Mostafa A Borahay, Mehmet R Asoglu, Aymara Mas, Sarah Adam, Gokhan S Kilic, Ayman Al-Hendy
Uterine fibroids are the most common gynecologic tumors with a significant medical and financial burden. Several genetic, hormonal, and biological factors have been shown to contribute to the development and growth of fibroid tumors. Of these factors, estrogen is particularly critical since fibroids are considered estrogen dependent because no prepubertal cases have been described in the literature and tumors tend to regress after menopause. Understanding the role of estrogen in fibroids is not only important for understanding the pathobiology of fibroids but also for the development of successful therapeutics...
November 20, 2016: Reproductive Sciences
Wenwen Gu, Nian Dong, Peng Wang, Changgen Shi, Jun Yang, Jian Wang
The drug resistance and tumor metastasis have been the main obstacles for the longer-term therapeutic effects of tamoxifen (TAM) on estrogen receptor-positive (ER(+)) breast cancer, but the mechanisms underlying the TAM resistance are still unclear. Here, we demonstrated that the membrane-associated estrogen receptor ER-α36 signaling, but not the G protein-coupled estrogen receptor 1 (GPER1) signaling, might be involved in the TAM resistance and metastasis of breast cancer cells. In this study, a model of ER(+) breast cancer cell MCF-7 that involves the up-regulated expression of ER-α36 and unchanged expression of ER-α66 and GPER1 was established via the removal of insulin from the cell culture medium...
November 11, 2016: Cell Biology and Toxicology
Fan Yang, Zhi-Min Shao
G protein-coupled estrogen receptor 1 (GPER1) is widely expressed in breast cancer; however, its prognostic significance in breast cancer patients remains controversial. In this study, expression levels of GPER1 were analyzed by using real-time polymerase chain reaction in 167 primary breast cancer samples, and overall survival (OS), recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS) were analyzed by using Kaplan-Meier curves and multivariable Cox regression...
2016: OncoTargets and Therapy
Tetsuo Mitsui, Maho Ishida, Michi Izawa, Jun Arita
Estrogen binds to nuclear estrogen receptors (ERs) to modulate transcription of target genes in estrogen-responsive cells. However, recent studies have shown that estrogen also binds to cytoplasmic membrane ERs to modulate protein kinase signaling cascades, leading to non-genomic actions. We investigated whether either nuclear or membrane ERs, including G protein-coupled estrogen receptor 1 (Gper1), mediate the inhibitory action of estrogen on insulin-like growth factor-1 (IGF-1)-induced proliferation of pituitary lactotrophs in primary culture...
October 19, 2016: Endocrine Journal
Andrée-Anne Poirier, Mélissa Côté, Mélanie Bourque, Marc Morissette, Thérèse Di Paolo, Denis Soulet
Motor symptoms in Parkinson's disease (PD) are often preceded by nonmotor symptoms related to dysfunctions of the autonomic nervous system such as constipation, defecatory problems, and delayed gastric emptying. These gastrointestinal impairments are associated with the alteration of dopaminergic (DAergic) neurons in the myenteric plexus of the gut. Recently, we demonstrated the anti-inflammatory properties of estrogens to treat intestinal neurodegeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD...
December 2016: Neurobiology of Aging
Olga Amelkina, Lina Zschockelt, Johanna Painer, Rodrigo Serra, Francisco Villaespesa, Eberhard Krause, Katarina Jewgenow, Beate C Braun
In contrast to the species studied, the corpus luteum (CL) of Iberian and Eurasian lynx physiologically persists in the ovary for more than 2 years and continues to secrete progesterone. Such persistent CL (perCL) transition into the next cycle and are present in the ovary together with the freshly formed CL (frCL) of a new ovulation. To date, the mechanisms supporting such CL persistence are not known. We analyzed the potential receptivity of feline CL to sex steroids through mRNA measurements of progesterone receptor (PGR), progesterone receptor membrane components (PGRMC) 1 and 2, estrogen receptor (ESR) 1 and ESR2, G protein-coupled estrogen receptor 1 (GPER1), and androgen receptor (AR)...
December 2016: Theriogenology
Yanlei Ji, Zhen Han, Limei Shao, Yuehuan Zhao
Estrogen has been closely associated with breast cancer. Several studies reported that Ca2+ signal and Ca2+ channels act in estrogen-modulated non-genomic pathway of breast cancer, however little was revealed on the function of L-type Ca2+ channels. The L-type Ca2+ channel subunit α 1D, named Cav1.3 was found in breast cancer cells. We aimed to investigate the expression and activity of Cav1.3 in human breast cancer, and reveal the effect of estrogen in regulating the expression of Cav1.3. The qRT-PCR and western blotting were employed to show that Cav1...
October 2016: Oncology Reports
Ebru Fındıklı, Mehmet Akif Camkurt, Mehmet Fatih Karaaslan, Ergul Belge Kurutas, Hatice Altun, Filiz İzci, Hüseyin Avni Fındıklı, Selçuk Kardas
Sex hormones, particularly estrogen, are suggested to play a role in the physiopathology of generalized anxiety disorder (GAD). Estrogen functions through the estrogen receptors alpha and beta and the recently discovered G protein-coupled estrogen receptor 1 (GPER1). This study aimed, for the first time, to evaluate serum GPER1 levels in drug-naive patients with GAD. This study included 40 newly diagnosed drug-naive patients with GAD aged between 18 and 50 years and 40 age- and gender-matched healthy controls...
October 30, 2016: Psychiatry Research
Qiang Cheng, Jia Meng, Xin-Shang Wang, Wen-Bo Kang, Zhen Tian, Kun Zhang, Gang Liu, Jian-Ning Zhao
Spinal cord injury (SCI) always occurs accidently and leads to motor dysfunction because of biochemical and pathological events. Estrogen has been shown to be neuroprotective against SCI through estrogen receptors (ERs), but the underlying mechanisms have not been fully elucidated. In the present study, we investigated the role of a newly found membrane ER, G protein-coupled estrogen receptor 1 (GPR30 or GPER1), and discussed the feasibility of a GPR30 agonist as an estrogen replacement. Forty adult female C57BL/6J mice (10-12 weeks old) were divided randomly into vehicle, G-1, E2, G-1 + G-15 and E2 + G-15 groups...
August 2016: Bioscience Reports
Amy Alexander, Andrew J Irving, Jenni Harvey
Estrogens play a key role in regulating reproductive and neuroendocrine function by activating classical nuclear steroid receptors that act as ligand gated transcription factors. However evidence is growing that estrogens also promote rapid non-genomic responses via activation of membrane-associated estrogen receptors. The G protein-coupled estrogen receptor (GPER1; also known as GPR30) has been identified as one of the main estrogen-sensitive receptors responsible for the rapid non-genomic actions of estrogen...
February 2017: Neuropharmacology
Tian-Zhi Zhao, Fei Shi, Jun Hu, Shi-Ming He, Qian Ding, Lian-Ting Ma
It is well-known that the neuroprotective effects of estrogen have potential in the prevention and amelioration of ischemic and degenerative neurological disorders, while the underlying mechanisms for estrogen actions are undefined. As an important mediator for the non-genomic functions of estrogen, GPER1 (G Protein-coupled Estrogen Receptor 1) has been suggested to involve in the beneficial roles of estrogen in neural cells. Here our studies on primary hippocampal neurons have focused on GPER1 in an in vitro model of ischemia using oxygen-glucose deprivation (OGD)...
July 22, 2016: Neuroscience
Anne Almey, Teresa A Milner, Wayne G Brake
Estrogens affect dopamine transmission in the striatum, increasing dopamine availability, maintaining D2 receptor density, and reducing the availability of the dopamine transporter. Some of these effects of estrogens are rapid, suggesting that they are mediated by membrane associated receptors. Recently our group demonstrated that there is extra-nuclear labeling for ERα, ERβ, and GPER1 in the striatum, but that ERα and GPER1 are not localized to dopaminergic neurons in this region. GABAergic neurons are the most common type of neuron in the striatum, and changes in GABA transmission affect dopamine transmission...
May 27, 2016: Neuroscience Letters
Nicholas J Evans, Asha L Bayliss, Vincenzina Reale, Peter D Evans
Estrogen can modulate neuronal development and signalling by both genomic and non-genomic pathways. Many of its rapid, non-genomic effects on nervous tissue have been suggested to be mediated via the activation of the estrogen sensitive G-protein coupled receptor (GPER1 or GPR30). There has been much controversy over the cellular location, signalling properties and endogenous activators of GPER1. Here we describe the pharmacology and signalling properties of GPER1 in an immortalized embryonic hippocampal cell line, mHippoE-18...
2016: PloS One
Akif Hakan Kurt, Fulsen Bozkus, Nuray Uremis, Muhammed Mehdi Uremis
Nephrotoxicity is an important problem during methotrexate (MTX) treatment, which has been widely used for the treatment of several cancer types. Females are less susceptible to kidney diseases; however, the reason for this condition has not to be fully clarified. But sex hormones such as estrogen may have a protective effect on the kidney. We aimed to evaluate the possible protective role of estrogen on the MTX-induced renal epithelial cell death. Primary renal proximal tubular epithelial cells (RPTEC) were incubated with MTX (1, 10 and 100 μM), either alone or in combination with the 17β-estradiol, G protein-coupled estrogen receptor 1 (GPER1) agonist G-1, estrogen receptor alpha agonist propyl pyrazole triol (PPT), estrogen receptor beta agonist diarylpropionitrile (DPN)...
June 2016: Renal Failure
Peter Oladimeji, Rebekah Skerl, Courtney Rusch, Maria Diakonova
Serine/threonine kinase PAK1 is activated by estrogen and plays an important role in breast cancer. However, the integration of PAK1 into the estrogen response is not fully understood. In this study, we investigated the mechanisms underlying the hormone-induced activation of estrogen receptor (ERα, ESR1). We show that estrogen activated PAK1 through both the ERα and GPER1 membrane receptors. Estrogen-dependent activation of PAK1 required the phosphorylation of tyrosine residues by Etk/Bmx and protein kinase A (PKA) within an assembled signaling complex comprising pTyr-PAK1, Etk/Bmx, the heterotrimer G-protein subunits Gβ1, Gγ2, and/or Gγ5, PAK-associated guanine nucleotide exchange factor (βPIX, ARHGEF7), and PKA...
May 1, 2016: Cancer Research
Johanna L Crimins, Athena Ching-Jung Wang, Frank Yuk, Rishi Puri, William G M Janssen, Yuko Hara, Peter R Rapp, John H Morrison
Age- and menopause-related impairment in working memory mediated by the dorsolateral prefrontal cortex (dlPFC) occurs in humans and nonhuman primates. Long-term cyclic 17β-estradiol treatment rescues cognitive deficits in aged ovariectomized rhesus monkeys while restoring highly plastic synapses. Here we tested whether distributions of G protein-coupled estrogen receptor 1 (GPER1) within monkey layer III dlPFC synapses are sensitive to age and estradiol, and coupled to cognitive function. Ovariectomized young and aged monkeys administered vehicle or estradiol were first tested on a delayed response test of working memory...
March 3, 2016: Cerebral Cortex
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