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Glucocorticoid receptor ( GR )

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https://www.readbyqxmd.com/read/29029225/glucocorticoid-signaling-in-health-and-disease-insights-from-tissue-specific-gr-knockout-mice
#1
Shannon Whirledge, Donald B DeFranco
Glucocorticoids are adrenally produced hormones critically involved in development, general physiology, and control of inflammation. Since their discovery, glucocorticoids have been widely utilized to treat a variety of inflammatory conditions. However, high doses or prolonged use leads to a number of side-effects throughout the body, which preclude their clinical utility. The primary actions of glucocorticoids are mediated by the glucocorticoid receptor (GR), a transcription factor that regulates many complex signaling pathways...
October 5, 2017: Endocrinology
https://www.readbyqxmd.com/read/29027256/integrated-in-silico-and-in-vivo-approaches-to-investigate-effects-of-bde-99-mediated-by-the-nuclear-receptors-on-developing-zebrafish
#2
Li Zhang, Yaru Jin, Zhihua Han, Hongling Liu, Laihao Shi, Xiaoxue Hua, Jon A Doering, Song Tang, John P Giesy, Hongxia Yu
BDE-99 is one of the most abundant PBDEs, which due to its potential persistence and bioaccumulation occurs in aquatic wildlife. Previous studies in mammals have shown that BDE-99 affected development and disrupted certain endocrine functions through signaling pathways mediated by nuclear receptors (NRs). However, fewer studies have investigated the potential of BDE-99 to interact with NRs in aquatic vertebrates, such as fish. In the present study, interactions between BDE-99 and NRs were investigated by use of in silico and in vivo approaches...
October 12, 2017: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/29025979/the-melatonin-receptor-agonist-piromelatine-ameliorates-impaired-glucose-metabolism-in-chronically-stressed-rats-fed-a-high-fat-diet
#3
Jun Zhou, Deng Wang, Xiaohong Luo, Xu Jia, Maoxing Li, Laudon Moshe, Ruxue Zhang, Zhengping Jia
Modern lifestyle factors (high-caloric food rich in fat) and daily chronic stress are important risk factors for metabolic disturbances. Increased hypothalamic-pituitary-adrenal (HPA) axis activity and the subsequent excess production of glucocorticoids (GCs) in response to chronic stress (CS) leads to increases in metabolic complications, such as type 2 diabetes and insulin resistance (IR). Melatonin (MLT), which protects several regulatory components of the HPA axis from GC-induced deterioration, might improve glucose homeostasis...
October 12, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29024676/perinatal-fluoxetine-prevents-the-effect-of-pre-gestational-maternal-stress-on-5-ht-in-the-pfc-but-maternal-stress-has-enduring-effects-on-mpfc-synaptic-structure-in-offspring
#4
Mary Gemmel, Nikolaos Kokras, Christina Dalla, Jodi L Pawluski
Maternal affective disorders are frequently treated with selective serotonin reuptake inhibitor medications (SSRIs); with up to 10% of women being prescribed these medications during pregnancy. Infant development depends on the early serotonergic environment, which is altered by perinatal SSRIs, raising concern about how these medications affect neural outcomes. While clinical and preclinical research suggests an impact of SSRIs on the developing brain, more research is needed to determine the effects on neuroplasticity, the serotonergic system, and the hypothalamic-pituitary-adrenal axis in neural regions mediating behavior...
October 9, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29021694/korean-red-ginseng-extract-induces-angiogenesis-through-activation-of-glucocorticoid-receptor
#5
Wai-Nam Sung, Hoi-Hin Kwok, Man-Hee Rhee, Patrick Ying-Kit Yue, Ricky Ngok-Shun Wong
BACKGROUND: Our previous studies have demonstrated that ginsenoside-Rg1 can promote angiogenesis in vitro and in vivo through activation of the glucocorticoid receptor (GR). Furthermore, microRNA (miRNA) expression profiling has shown that Rg1 can modulate the expression of a subset of miRNAs to induce angiogenesis. Moreover, Rb1 was shown to be antiangiogenic through activation of a different pathway. These studies highlight the important functions of miRNAs on ginseng-regulated physiological processes...
October 2017: Journal of Ginseng Research
https://www.readbyqxmd.com/read/28993273/acute-mental-stress-induces-mitochondrial-bioenergetic-crisis-and-hyper-fission-along-with-aberrant-mitophagy-in-the-gut-mucosa-in-rodent-model-of-stress-related-mucosal-disease
#6
Rudranil De, Somnath Mazumder, Souvik Sarkar, Subhashis Debsharma, Asim Azhar Siddiqui, Shubhra Jyoti Saha, Chinmoy Banerjee, Shiladitya Nag, Debanjan Saha, Uday Bandyopadhyay
Psychological stress, depression and anxiety lead to multiple organ dysfunctions wherein stress-related mucosal disease (SRMD) is common to people experiencing stress and also occur as a side effect in patients admitted to intensive care units; however the underlying molecular aetiology is still obscure. We report that in rat-SRMD model, cold restraint-stress severely damaged gut mitochondrial functions to generate superoxide anion (O2(•-)), depletion of ATP and shifted mitochondrial fission-fusion dynamics towards enhanced fission to induce mucosal injury...
October 6, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28986096/high-fat-diet-enhances-hepatic-ischemia-reperfusion-injury-induced-apoptosis-role-of-glucocorticoid-receptors
#7
Huan-Qiu Liu, Rui-Jun Li, Xin Sun, Ji Li
AIMS: The present study was designed to evaluate whether and how glucocorticoids can affect obesity-regulated hepatic ischemia-reperfusion (I/R) injury. MAIN METHODS: To this end, we first examined whether hydrocortisone (HCT) has protective effects on liver damage induced by hepatic I/R injury in mice receiving high fat diet treatment. We then explored the role of GR expression and phosphorylation in the anti-apoptotic effects of hydrocortisone upon hepatic I/R injury...
October 3, 2017: Life Sciences
https://www.readbyqxmd.com/read/28984199/roles-of-alternative-splicing-in-modulating-transcriptional-regulation
#8
Jin Li, Yang Wang, Xi Rao, Yue Wang, Weixing Feng, Hong Liang, Yunlong Liu
BACKGROUND: The ability of a transcription factor to regulate its targets is modulated by a variety of genetic and epigenetic mechanisms. Alternative splicing can modulate gene function by adding or removing certain protein domains, and therefore affect the activity of protein. Reverse engineering of gene regulatory networks using gene expression profiles has proven valuable in dissecting the logical relationships among multiple proteins during the transcriptional regulation. However, it is unclear whether alternative splicing of certain proteins affects the activity of other transcription factors...
October 3, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28984075/association-of-glucocorticoid-receptor-gene-polymorphisms-with-systemic-lupus-erythematosus-in-a-chinese-population
#9
Yang-Fan Chen, Jian-Hua Xu, Yan-Feng Zou, Li Lian, Fen Wang, Shan-Yu Chen, Jing Cai, Mu Li
OBJECTIVES: To identify the association of glucocorticoid receptor (GR) gene polymorphism with systemic lupus erythematosus (SLE). METHODS: A case-control study was carried out, in which 400 Chinese patients with SLE and 400 normal people were enrolled. DNA was extracted using a genomic DNA extraction kit, and tagged single nucleotide polymorphisms (SNPs) were identified by Haploview (4.0) Project from the Chinese HapMap Project. Eighteen tagged SNPs of the GR gene were genotyped by the Multiplex SNaPshot technique...
October 6, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28978062/dexamethasone-affects-cell-growth-apoptosis-chemosensitivity-of-colon-cancer-via-glucocorticoid-receptor-%C3%AE-nf-%C3%AE%C2%BAb
#10
Jianming He, Jinming Zhou, Weiwen Yang, Qi Zhou, Xi Liang, Xueli Pang, Jianjun Li, Feng Pan, Houjie Liang
Glucocorticoids are effective to treat lymphoma and leukemia. Their effect in colon cancer remains far from clear. Here, we found that glucocorticoid receptor (GR) α protein level was dramatically lower in colon cancer than in lymphoma. Colon cell lines LoVo and HCT116 were GRα-rich and GRα was not detectable in HT29 or SW480. Dexamethasone significantly inhibited cell growth of GRα-rich cell lines and did not significantly affect GRα-negative cell lines. Dexamethasone induced apoptosis and increased chemosensitivity of GRα-rich cell lines...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28969550/21-hydroxy-6-19-epoxyprogesterone-a-promising-therapeutic-agent-and-a-molecular-tool-for-deciphering-glucocorticoid-action
#11
Adali Pecci, Lautaro D Alvarez, Diego M Presman, Gerardo Burton
Glucocorticoids are steroid hormones that exert most of their effects through their binding to the glucocorticoid receptor (GR), a ligand regulated transcription factor. Although glucocorticoids are widely used in the clinic, their usage in chronic therapies provokes severe adverse reactions. In the quest for safer glucocorticoids a dissociated model was established that proposes a disconnection between GR activated pathways responsible of desired pharmacological effects and pathways involved in adverse GR reactions...
October 2, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/28968829/the-ns1-protein-of-respiratory-syncytial-virus-blocks-glucocorticoid-receptor-nuclear-translocation-by-targeting-ipo13-may-account-for-glucocorticoid-insensitive
#12
Jun Xie, Xiaoru Long, Leiqiong Gao, Sisi Chen, Keting Zhao, Wei Li, Na Zhou, Na Zang, Yu Deng, Luo Ren, Lijia Wang, Zhengxiu Luo, Wenwei Tu, Xiaodong Zhao, Zhou Fu, Xiaohong Xie, Enmei Liu
In spite of their powerful anti-inflammatory effect, glucocorticoids have shown no significant clinical benefit in respiratory syncytial virus (RSV)-induced bronchiolitis, the reason for which remains unclear. Upon glucocorticoid binding, the cytoplasmic glucocorticoid receptor (GR) translocates to the nucleus with the help of importin-13 (IPO13). Here, we report that RSV infection reduced GR nuclear translocation in the nasopharyngeal aspirate (NPA) of the RSV-infected infants, lungs of infected mice, and A549 cells, which coincided with decreased IPO13 expression...
September 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28965332/adaptor-protein-appl2-affects-adult-antidepressant-behaviors-and-hippocampal-neurogenesis-via-regulating-the-sensitivity-of-glucocorticoid-receptor
#13
Chong Gao, Xingmiao Chen, Aimin Xu, Kenneth Cheng, Jiangang Shen
Adaptor proteins containing the pleckstrin homology domain, phosphotyrosine binding domain, and leucine zipper motif (APPLs) are multifunctional adaptor proteins involved in regulating many biological activities and processes. The newly identified metabolic factor APPL2 showed the potentials to modulate cell growth, but whether APPL2 could affect adult neurogenesis and animal mood behaviors remains unknown. In the present study, APPL2 transgenic (Tg) mice and wild-type littermates were used for testing our hypothesis that APPL2 could affect glucocorticoid receptor (GR) signaling and modulate hippocampal neurogenesis, which contributes to depressive and anxiety behaviors...
September 30, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28955999/a-novel-human-glucocorticoid-receptor-snp-results-in-increased-transactivation-potential
#14
Tajia L Green, Kelly Tung, Debora Lim, Stacey M Leventhal, Kiho Cho, David G Greenhalgh
Glucocorticoids are one of the most widely used therapeutics in the treatment of a variety of inflammatory disorders. However, it is known that there are variable patient responses to glucocorticoid treatment; there are responders and non-responders, or those that need higher dosages. Polymorphisms in the glucocorticoid receptor (GR) have been implicated in this variability. In this study, ninety-seven volunteers were surveyed for polymorphisms in the human GR-alpha (hGRα), the accepted biologically active reference isoform...
March 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28954735/bcli-polymorphism-of-the-glucocorticoid-receptor-and-adrenal-crisis-in-primary-adrenal-insufficiency
#15
Kathrin Zopf, Kathrin Frey, Tina Kienitz, Manfred Ventz, Britta Bauer, Marcus Quinkler
CONTEXT: Patients with primary adrenal insufficiency (PAI) or congenital adrenal hyperplasia (CAH) are at high risk of adrenal crisis (AC). Glucocorticoid sensitivity is at least partially genetically determined by polymorphisms of the glucocorticoid receptor (GR). OBJECTIVES: To determine if number of intercurrent illnesses and AC are associated with the GR gene polymorphism BclI in patients with PAI and CAH. DESIGN AND PATIENTS: This prospective, longitudinal study over 37...
September 27, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28949968/normalisation-of-surfactant-protein-a-and-b-expression-in-the-lungs-of-low-birth-weight-lambs-by-21-days-old
#16
Jia Yin Soo, Sandra Orgeig, Erin Victoria McGillick, Song Zhang, I Caroline McMillen, Janna L Morrison
Intrauterine growth restriction (IUGR) induced by placental restriction (PR) in the sheep negatively impacts lung and pulmonary surfactant development during fetal life. Using a sheep model of low birth weight (LBW), we found that there was an increase in mRNA expression of surfactant protein (SP)-A, -B and -C in the lung of LBW lambs but no difference in the protein expression of SP-A or -B. LBW also resulted in increased lysosome-associated membrane glycoprotein (LAMP)-3 mRNA expression, which may indicate an increase in either the density of type II Alveolar epithelial cells (AEC) or maturity of type II AECs...
2017: PloS One
https://www.readbyqxmd.com/read/28942102/skov3-cells-containing-a-truncated-arid1a-protein-have-a-restricted-genome-wide-response-to-glucocorticoids
#17
F E Stubbs, M T Birnie, S C Biddie, S L Lightman, B L Conway-Campbell
AT-rich interacting domain subunit 1a (ARID1a) is an essential SWI/SNF component frequently mutated in human cancers. ARID1a mutations have also been associated with glucocorticoid resistance, potentially related to the well-established role of the SWI/SNF complex in glucocorticoid target gene regulation. Glucocorticoids are steroid hormones important for regulating many physiological processes through the activation of the glucocorticoid receptor (GR). As GR interacts directly with ARID1a, we hypothesized that a truncating ARID mutation would interfere with GR-dependent gene regulation...
September 20, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28941781/glucocorticoids-and-toll-like-receptor-2-cooperatively-induce-acute-phase-serum-amyloid-a
#18
Qi Su, Günther Weindl
Serum amyloid A (SAA) is a highly conserved acute-phase protein and extrahepatic produced SAA1/2 contributes to cutaneous inflammation. Prolonged systemic or topical treatment with glucocorticoids can provoke skin diseases such as steroid-induced acne. Glucocorticoids increase Toll-like receptor 2 (TLR2) expression, however, an inflammatory mediator linked to this side effect remains elusive. We report that TLR2 agonists in combination with dexamethasone substantially increase SAA expression and production in human keratinocytes and epithelial cells...
September 20, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28941573/hypothalamic-pituitary-adrenal-axis-responsiveness-to-methamphetamine-is-modulated-by-gonadectomy-in-males
#19
Jason S Jacobskind, Zachary J Rosinger, Damian G Zuloaga
Sex differences in patterns of methamphetamine (MA) abuse have been reported with females (humans and rodents) showing an elevated addiction phenotype. Previous findings indicate MA-induced hypothalamic-pituitary-adrenal (HPA) axis activation is also sexually dimorphic with females exhibiting an elevated glucocorticoid release and differential neural activation patterns within HPA axis-associated brain regions. These effects may contribute to sex differences in abuse. To determine the role of gonadal hormones in mediating sex differences in MA-induced glucocorticoids, male and female C57BL/6J mice were gonadectomized or sham-operated, and following recovery, injected with MA (5 mg/kg) and sacrificed 60 minutes or 120 minutes later...
September 20, 2017: Brain Research
https://www.readbyqxmd.com/read/28938459/selective-glucocorticoid-receptor-antagonist-cort125281-activates-brown-adipose-tissue-and-alters-lipid-distribution-in-male-mice
#20
Jan Kroon, Lisa L Koorneef, Jose K van den Heuvel, Cristy R C Verzijl, Nienke M van de Velde, Isabel M Mol, Hetty C M Sips, Hazel Hunt, Patrick C N Rensen, Onno C Meijer
Glucocorticoids influence a wide range of metabolic processes in the human body and excessive glucocorticoid exposure is known to contribute to the development of metabolic disease. We evaluated the utility of the novel glucocorticoid receptor (GR) antagonist CORT125281 for its potential to overcome adiposity, glucose intolerance and dyslipidaemia, and compared this head-to-head with classic GR antagonist RU486 (mifepristone). We show that, while RU486 displays cross-reactivity to the progesterone and androgen receptor, CORT125281 selectively inhibits GR transcriptional activity...
September 18, 2017: Endocrinology
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