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Glucocorticoid receptor ( GR )

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https://www.readbyqxmd.com/read/28102225/glucocorticoid-receptor-signalling-activates-yap-in-breast-cancer
#1
Giovanni Sorrentino, Naomi Ruggeri, Alessandro Zannini, Eleonora Ingallina, Rebecca Bertolio, Carolina Marotta, Carmelo Neri, Elisa Cappuzzello, Mattia Forcato, Antonio Rosato, Miguel Mano, Silvio Bicciato, Giannino Del Sal
The Hippo pathway is an oncosuppressor signalling cascade that plays a major role in the control of cell growth, tissue homoeostasis and organ size. Dysregulation of the Hippo pathway leads to aberrant activation of the transcription co-activator YAP (Yes-associated protein) that contributes to tumorigenesis in several tissues. Here we identify glucocorticoids (GCs) as hormonal activators of YAP. Stimulation of glucocorticoid receptor (GR) leads to increase of YAP protein levels, nuclear accumulation and transcriptional activity in vitro and in vivo...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28096435/regulation-of-aldosterone-secretion-by-mineralocorticoid-receptor-mediated-signaling
#2
Cherish Chong, Anis Hamid, Tham Yao, Amanda Garza, Luminita Pojoga, Gail K Adler, Jose R Romero, Gordon H Williams
We posit the existence of a paracrine/autocrine negative feedback loop, mediated by the mineralocorticoid receptor (MR), regulating aldosterone secretion. To assess this hypothesis we asked whether altering MR activity in zona glomerulosa (ZG) cells affects aldosterone production. To this end, we studied ex vivo ZG cells isolated from male Wistar rats fed chow containing either high (1.6% Na+ [HS]) or low (0.03% Na+ [LS]) amount of sodium. Western blot analyses demonstrated that MR was present in both the ZG and zona fasciculata/zona reticularis (ZF/ZR/ZR)...
January 17, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28096152/bcli-glucocorticoid-receptor-polymorphism-in-relation-to-arterial-stiffening-and-cardiac-structure-and-function-the-hoorn-and-codam-studies
#3
Dirk van Moorsel, Ronald M Henry, Nicolaas C Schaper, Marleen M van Greevenbroek, Elisabeth F van Rossum, Leen M 't Hart, Casper G Schalkwijk, Carla J van der Kallen, Jacqueline M Dekker, Coen D Stehouwer, Bas Havekes
BACKGROUND: Chronic glucocorticoid excess is associated with arterial stiffening and cardiac dysfunction. The BclI glucocorticoid receptor (GR) polymorphism increases GR sensitivity and is associated with a higher body mass index (BMI) and some proxies for cardiovascular disease (CVD). Whether BclI influences arterial stiffening and cardiac dysfunction is currently unknown. Therefore, the aim of the present study was to investigate the association of the BclI polymorphism with arterial stiffening and cardiac structure and function...
January 17, 2017: American Journal of Hypertension
https://www.readbyqxmd.com/read/28093219/a-mixed-glucocorticoid-mineralocorticoid-receptor-modulator-dampens-endocrine-and-hippocampal-stress-responsivity-in-male-rats
#4
Elizabeth T Nguyen, Joshua Streicher, Sarah Berman, Jody L Caldwell, Valentina Ghisays, Christina M Estrada, Aynara C Wulsin, Matia B Solomon
Aberrant glucocorticoid secretion is implicated in the pathophysiology of stress-related disorders (i.e., depression, anxiety). Glucocorticoids exert biological effects via mineralocorticoid (MR) and glucocorticoid (GR) receptors. Previous data from our laboratory indicate that GR antagonism/modulation (i.e., mifepristone, CORT 108297) regulate endocrine, behavioral, and central stress responses. Because of the dynamic interplay between MR and GR on HPA axis regulation and emotionality, compounds targeting both receptors are of interest for stress-related pathology...
January 13, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28089704/brain-mineralocorticoid-receptor-function-in-control-of-salt-balance-and-stress-adaptation
#5
REVIEW
E Ronald de Kloet, Marian Joëls
We will highlight in honor of Randall Sakai the peculiar characteristics of the brain mineralocorticoid receptor (MR) in its response pattern to the classical mineralocorticoid aldosterone and the naturally occurring glucocorticoids corticosterone and cortisol. Neurons in the nucleus tractus solitarii (NTS) express MR, which mediate selectively the action of aldosterone on salt appetite, sympathetic outflow and volume regulation. The MR-containing NTS neurons innervate limbic-forebrain circuits enabling aldosterone to also modulate reciprocally arousal, motivation, fear and reward...
January 13, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28089628/crf1-but-not-glucocorticoid-receptor-antagonists-reduce-separation-induced-distress-vocalizations-in-guinea-pig-pups-and-crf-overexpressing-mouse-pups-a-combination-study-with-paroxetine
#6
P Monika Verdouw, Joantine C J van Esterik, Bernard W M M Peeters, Mark J Millan, Lucianne Groenink
RATIONALE: Given the large number of patients that does not respond sufficiently to currently available treatment for anxiety disorders, there is a need for improved treatment. OBJECTIVES: We evaluated the anxiolytic effects of corticotropin releasing factor (CRF)1 receptor antagonists and glucocorticoid receptor (GR) antagonists in the separation-induced vocalization test in guinea pigs and transgenic mice with central CRF overexpression. Furthermore, we explored effects of these drugs when given in combination with a suboptimal dose of a selective serotonin re-uptake inhibitor (SSRI)...
January 12, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28088388/activation-of-gr-but-not-pxr-by-dexamethasone-attenuated-acetaminophen-hepatotoxicities-via-fgf21-induction
#7
Saurabh G Vispute, Pengli Bu, Yuan Le, Xingguo Cheng
Glucocorticoid receptor (GR) signaling is indispensable for cell growth and development, and plays important roles in drug metabolism. Fibroblast growth factor (Fgf) 21, an important regulator of glucose, lipid, and energy metabolism, plays a cytoprotective role by attenuating toxicities induced by chemicals such as dioxins, acetaminophen (APAP), and alcohols. The present study investigates the impact of dexamethasone (DEX)-activated GR on Fgf21 expression and how it affects the progression of APAP-induced hepatotoxicity...
January 11, 2017: Toxicology
https://www.readbyqxmd.com/read/28086911/enhanced-neuroinflammation-mediated-by-dna-methylation-of-the-glucocorticoid-receptor-triggers-cognitive-dysfunction-after-sevoflurane-anesthesia-in-adult-rats-subjected-to-maternal-separation-during-the-neonatal-period
#8
Yangzi Zhu, Yu Wang, Rui Yao, Ting Hao, Junli Cao, He Huang, Liwei Wang, Yuqing Wu
BACKGROUND: Mounting evidence indicates that children who experience abuse and neglect are prone to chronic diseases and premature mortality later in life. One mechanistic hypothesis for this phenomenon is that early life adversity alters the expression or functioning of the glucocorticoid receptor (GR) throughout the course of life and thereby increases sensitivity to inflammatory stimulation. An exaggerated pro-inflammatory response is generally considered to be a key cause of postoperative cognitive dysfunction (POCD)...
January 7, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28078411/in-vitro-and-in-silico-assessment-of-the-structure-dependent-binding-of-bisphenol-analogues-to-glucocorticoid-receptor
#9
Jie Zhang, Tiehua Zhang, Tianzhu Guan, Hansong Yu, Tiezhu Li
Widespread use of bisphenol A (BPA) and other bisphenol analogues has attracted increasing attention for their potential adverse effects. As environmental endocrine-disrupting compounds (EDCs), bisphenols (BPs) may activate a variety of nuclear receptors, including glucocorticoid receptor (GR). In this work, the binding of 11 BPs to GR was investigated by fluorescence polarization (FP) assay in combination with molecular dynamics simulations. The human glucocorticoid receptor was prepared as a soluble recombinant protein...
January 11, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28076749/epigenetic-changes-of-hepatic-glucocorticoid-receptor-in-sheep-male-offspring-undernourished-in-utero
#10
Stella Chadio, Basiliki Kotsampasi, Stylliani Taka, Emmanouil Liandris, Nikolaos Papadopoulos, Elias Plakokefalos
The aim of this study was to characterise the effects of maternal undernutrition during gestation on hepatic gluconeogenic enzyme gene expression and to determine whether such effects are mediated through epigenetic changes in the glucocorticoid receptor (GR). Pregnant ewes were fed a 50% nutrient-restricted diet from Day 0 to 30 (R1) or from Day 31 to 100 of gestation (R2) or a 100% diet throughout gestation (Control). After parturition lambs were fed to appetite. At 10 months of age offspring were euthanised and livers were removed...
January 12, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28069826/endostatin-inhibits-androgen-independent-prostate-cancer-growth-by-suppressing-nuclear-receptor-mediated-oxidative-stress
#11
Joo Hyoung Lee, Minsung Kang, Hong Wang, Gurudatta Naik, James A Mobley, Guru Sonpavde, W Timothy Garvey, Victor M Darley-Usmar, Selvarangan Ponnazhagan
Androgen-deprivation therapy has been identified to induce oxidative stress in prostate cancer (PCa), leading to reactivation of androgen receptor (AR) signaling in a hormone-refractory manner. Thus, antioxidant therapies have gained attention as adjuvants for castration-resistant PCa. Here, we report for the first time that human endostatin (ES) prevents androgen-independent growth phenotype in PCa cells through its molecular targeting of AR and glucocorticoid receptor (GR) and downstream pro-oxidant signaling...
January 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28069032/glucocorticoid-receptor-gene-polymorphisms-in-hereditary-angioedema-with-c1-inhibitor-deficiency
#12
Zsuzsanna Zotter, Zsolt Nagy, Attila Patócs, Dorottya Csuka, Nóra Veszeli, Kinga Viktória Kőhalmi, Henriette Farkas
BACKGROUND: Hereditary angioedema caused by C1-inhibitor deficiency (C1-INH-HAE) is a rare, autosomal dominant disorder. C1-INH-HAE is characterized by edema-formation, which may occur in response to stress. The individual's response to stress stimuli is partly genetically determined. Activation of the hypothalamic-pituitary-adrenal axis results in the release of cortisol. In turn, the secreted gluco- and mineralocorticoids affect the metabolism, as well as the cardiovascular and immune systems...
January 10, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28063130/glucocorticoids-curtail-stimuli-induced-creb-phosphorylation-in-trh-neurons-through-interaction-of-the-glucocorticoid-receptor-with-the-catalytic-subunit-of-protein-kinase-a
#13
Israim Sotelo-Rivera, Antonieta Cote-Vélez, Rosa-María Uribe, Jean-Louis Charli, Patricia Joseph-Bravo
PURPOSE: Corticosterone prevents cold-induced stimulation of thyrotropin-releasing hormone (Trh) expression in rats, and the stimulatory effect of dibutyryl cyclic-adenosine monophosphate (dB-cAMP) on Trh transcription in hypothalamic cultures. We searched for the mechanism of this interference. METHODS: Immunohistochemical analyses of phosphorylated cAMP-response element binding protein (pCREB) were performed in the paraventricular nucleus (PVN) of Wistar rats, and in cell cultures of 17-day old rat hypothalami, or neuroblastoma SH-SY5Y cells...
January 6, 2017: Endocrine
https://www.readbyqxmd.com/read/28060336/screening-for-endocrine-activity-in-water-using-commercially-available-in-vitro-transactivation-bioassays
#14
Alvine C Mehinto, B Sumith Jayasinghe, Darcy R Vandervort, Nancy D Denslow, Keith A Maruya
In vitro transactivation bioassays have shown promise as water quality monitoring tools, however their adoption and widespread application has been hindered partly due to a lack of standardized methods and availability of robust, user-friendly technology. In this study, commercially available, division-arrested cell lines were employed to quantitatively screen for endocrine activity of chemicals present in water samples of interest to environmental quality professionals. A single, standardized protocol that included comprehensive quality assurance/quality control (QA/QC) checks was developed for Estrogen and Glucocorticoid Receptor activity (ER and GR, respectively) using a cell-based Fluorescence Resonance Energy Transfer (FRET) assay...
December 4, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28057868/glucocorticoid-receptor-alters-isovolumetric-contraction-and-restrains-cardiac-fibrosis
#15
Rachel Richardson, Emma Batchen, Adrian Thomson, Rowan Darroch, Xinlu Pan, Eva Rog-Zielinska, Wiktoria Wyrzykowska, Kathleen Scullion, Emad A S Al-Dujaili, Mary Diaz, Carmel Moran, Chris J Kenyon, Gillian A Gray, Karen Chapman
Corticosteroids directly affect the heart and vasculature and are implicated in the pathogenesis of heart failure. Attention has focussed upon the role of the mineralocorticoid receptor (MR) in mediating pro-fibrotic and other adverse effects of corticosteroids upon the heart. In contrast, the role of the glucocorticoid receptor (GR) in the heart and vasculature is less well understood. We addressed this in mice with cardiomyocyte and vascular smooth muscle deletion of GR (SMGRKO mice). Survival of SMGRKO mice to weaning was reduced compared with littermate controls...
January 5, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28056052/the-glucocorticoid-receptor-regulates-the-angptl4-gene-in-a-ctcf-mediated-chromatin-context-in-human-hepatic-cells
#16
Masafumi Nakamoto, Ko Ishihara, Takehisa Watanabe, Akiyuki Hirosue, Shinjiro Hino, Masanori Shinohara, Hideki Nakayama, Mitsuyoshi Nakao
Glucocorticoid signaling through the glucocorticoid receptor (GR) plays essential roles in the response to stress and in energy metabolism. This hormonal action is integrated to the transcriptional control of GR-target genes in a cell type-specific and condition-dependent manner. In the present study, we found that the GR regulates the angiopoietin-like 4 gene (ANGPTL4) in a CCCTC-binding factor (CTCF)-mediated chromatin context in the human hepatic HepG2 cells. There are at least four CTCF-enriched sites and two GR-binding sites within the ANGPTL4 locus...
2017: PloS One
https://www.readbyqxmd.com/read/28053348/glucocorticoid-receptor-control-of-transcription-precision-and-plasticity-via-allostery
#17
Emily R Weikum, Matthew T Knuesel, Eric A Ortlund, Keith R Yamamoto
The glucocorticoid receptor (GR) is a constitutively expressed transcriptional regulatory factor (TRF) that controls many distinct gene networks, each uniquely determined by particular cellular and physiological contexts. The precision of GR-mediated responses seems to depend on combinatorial, context-specific assembly of GR-nucleated transcription regulatory complexes at genomic response elements. In turn, evidence suggests that context-driven plasticity is conferred by the integration of multiple signals, each serving as an allosteric effector of GR conformation, a key determinant of regulatory complex composition and activity...
January 5, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28049829/glucocorticoid-receptor-in-t-cells-mediates-protection-from-autoimmunity-in-pregnancy
#18
Jan Broder Engler, Nina Kursawe, María Emilia Solano, Kostas Patas, Sabine Wehrmann, Nina Heckmann, Fred Lühder, Holger M Reichardt, Petra Clara Arck, Stefan M Gold, Manuel A Friese
Pregnancy is one of the strongest inducers of immunological tolerance. Disease activity of many autoimmune diseases including multiple sclerosis (MS) is temporarily suppressed by pregnancy, but little is known about the underlying molecular mechanisms. Here, we investigated the endocrine regulation of conventional and regulatory T cells (Tregs) during reproduction. In vitro, we found the pregnancy hormone progesterone to robustly increase Treg frequencies via promiscuous binding to the glucocorticoid receptor (GR) in T cells...
January 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28031249/transcription-factor-assisted-loading-and-enhancer-dynamics-dictate-the-hepatic-fasting-response
#19
Ido Goldstein, Songjoon Baek, Diego M Presman, Ville Pakkinaho, Erin E Swinstead, Gordon L Hager
Fasting elicits transcriptional programs in hepatocytes leading to glucose and ketone production. This transcriptional program is regulated by many transcription factors (TFs). To understands how this complex network regulates the metabolic response to fasting we aimed at isolating the enhancers and TFs dictating it. Measuring chromatin accessibility revealed that fasting massively reorganizes liver chromatin, exposing numerous fasting-induced enhancers. By utilizing computational methods in combination with dissecting enhancers features and TF cistromes, we implicated four key TFs regulating the fasting response: glucocorticoid receptor (GR), cAMP responsive element binding protein 1 (CREB1), peroxisome proliferator activated receptor alpha (PPARA) and CCAAT/enhancer binding protein beta (CEBPB)...
December 28, 2016: Genome Research
https://www.readbyqxmd.com/read/28030791/dexamethasone-induces-docetaxel-and-cisplatin-resistance-partially-through-up-regulating-kr%C3%A3-ppel-like-factor-5-in-triple-negative-breast-cancer
#20
Zhen Li, Jian Dong, Tianning Zou, Chengzhi Du, Siyuan Li, Ceshi Chen, Rong Liu, Kunhua Wang
PURPOSE: Dexamethasone (Dex), a glucocorticoid (GC), is used as a pretreatment drug in cancer patients undergoing chemotherapy. Dex functions by binding to the glucocorticoid receptor (GR) to prevent allergic reactions and severe chemotherapeutic side effects such as nausea and vomiting. However, the mechanisms by which Dex causes chemoresistance remain unknown. METHODS: We used docetaxel and cisplatin to treat triple-negative breast cancer (TNBC) cells with or without Dex and assessed cell proliferation using a sulforhodamine B colorimetric (SRB) assay...
December 24, 2016: Oncotarget
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