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Glucocorticoid receptor ( GR )

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https://www.readbyqxmd.com/read/28432191/gene-expression-effects-of-glucocorticoid-and-mineralocorticoid-receptor-agonists-and-antagonists-on-normal-human-skeletal-muscle
#1
Jessica A Chadwick, James Spencer Hauck, Celso E Gomez-Sanchez, Elise P Gomez-Sanchez, Jill A Rafael-Fortney
Mineralocorticoid and glucocorticoid receptors are closely related steroid hormone receptors that regulate gene expression through many of the same hormone response elements. However, their transcriptional activities and effects in skeletal muscles are largely unknown. We recently identified mineralocorticoid receptors (MR) in skeletal muscles after finding that combined treatment with the angiotensin-converting enzyme inhibitor lisinopril and MR antagonist spironolactone was therapeutic in Duchenne muscular dystrophy mouse models...
April 21, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28430805/effect-of-the-glucocorticoid-receptor-antagonist-ru486-on-mk-801-induced-behavioural-sensitisation
#2
Emilia M Lefevre, Gregory A Medley, Timothy Reeks, Suzy Alexander, Thomas H J Burne, Darryl W Eyles
Stress is known to modulate sensitisation to repeated psychostimulant exposure. However, there is no direct evidence linking glucocorticoids and sensitisation achieved by repeated administration of the NMDA receptor antagonist MK-801. We tested the hypothesis that co-administration of RU486, a glucocorticoid receptor (GR) antagonist, prior to repeated daily MK-801 injections would block the expression of locomotor sensitisation due to its dual effects on corticosterone and dopamine. We employed a repeated MK-801 administration locomotor sensitisation paradigm in male Sprague Dawley rats...
2017: PloS One
https://www.readbyqxmd.com/read/28430429/potential-glucocorticoid-and-mineralocorticoid-effects-of-nine-organophosphate-flame-retardants
#3
Quan Zhang, Jinghua Wang, Jianqiang Zhu, Jing Liu, Meirong Zhao
Organophosphate flame retardants (OPFRs), as alternatives of polybrominated diphenyl ethers (PBDEs), have been frequently detected in the environment and biota, and could pose adverse effects on organisms. However, information on the potential endocrine disruption of OPFRs, especially their effects on steroid hormone receptors, such as glucocorticoid and mineralocorticoid receptors (GR/MR), is limited. In this study, the dual-luciferase reporter gene assay via GR/MR and a H295R steroidogenesis assay were employed to evaluate the endocrine disruption of nine OPFRs...
April 21, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28428441/selective-glucocorticoid-receptor-modulators-sgrms-delay-castrate-resistant-prostate-cancer-growth
#4
Jacob Kach, Tiha M Long, Phillip Selman, Eva Y Tonsing-Carter, Maria A Bacalao, Ricardo R Lastra, Larischa de Wet, Shane Comiskey, Marc Gillard, Calvin VanOpstall, Diana C West, Wen-Ching Chan, Donald Vander Griend, Suzanne D Conzen, Russell Z Szmulewitz
Increased glucocorticoid receptor (GR) expression and activity following androgen blockade can contribute to castration-resistant prostate cancer (CRPC) progression. Therefore, we hypothesized that GR antagonism will have therapeutic benefit in CRPC. However, the FDA-approved nonselective, steroidal GR antagonist, mifepristone, lacks GR specificity, reducing its therapeutic potential. Here we report that two novel non-steroidal and highly selective GR modulators (SGRMs), CORT118335 and CORT108297, have the ability to block GR activity in prostate cancer (PC) and slow CRPC progression...
April 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28424165/suppression-of-b-cell-development-genes-is-key-to-glucocorticoid-efficacy-in-treatment-of-acute-lymphoblastic-leukemia
#5
Karina Kruth, Mimi Fang, Dawne N Shelton, Ossama Abu-Halawa, Ryan Mahling, Hongxing Yang, Jonathan S Weissman, Mignon L Loh, Markus Müschen, Sarah K Tasian, Michael C Bassik, Martin Kampmann, Miles A Pufall
Glucocorticoids (GCs), including dexamethasone (dex), are a central component of combination chemotherapy for childhood B-cell precursor acute lymphoblastic leukemia (B-ALL). GCs work by activating the glucocorticoid receptor (GR), a ligand-induced transcription factor, which in turn regulates genes that induce leukemic cell death. Which GR-regulated genes are required for GC cytotoxicity, which pathways affect their regulation, and how resistance arises are not well understood. Here we systematically integrate the transcriptional response of B-ALL to GCs with a next-generation shRNA screen to identify GC-regulated "effector" genes that contribute to cell death as well as genes that affect the sensitivity of B-ALL cells to dex...
April 19, 2017: Blood
https://www.readbyqxmd.com/read/28421158/cytotoxicity-of-zardaverine-in-embryonal-rhabdomyosarcoma-from-a-costello-syndrome-patient
#6
Donna M Cartledge, Katherine M Robbins, Katherine M Drake, Rachel Sternberg, Deborah L Stabley, Karen W Gripp, E Anders Kolb, Katia Sol-Church, Andrew D Napper
Costello syndrome (CS) patients suffer from a very high 10% incidence of embryonal rhabdomyosarcoma (ERMS). As tools to discover targeted therapeutic leads, we used a CS patient-derived ERMS cell line (CS242 ERMS) harboring a homozygous p.G12A mutation in HRAS, and a control cell line derived from the same patient comprising non-malignant CS242 fibroblasts with a heterozygous p.G12A HRAS mutation. A library of 2,000 compounds with known pharmacological activities was screened for their effect on CS242 ERMS cell viability...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28416324/e4bp4-mediates-glucocorticoid-regulated-adipogenesis-through-cox2
#7
Yang Yang, Hongkui Wei, Tongxing Song, Anle Cai, Yuanfei Zhou, Jie Peng, Siwen Jiang, Jian Peng
Adipogenesis is mediated by glucocorticoids via transcriptional regulation of glucocorticoid receptor (GR) target genes. However, the mechanism by which GR participates in adipogenesis has hitherto been poorly characterized. In this study, E4 promoter-binding protein 4 (E4BP4) was found to have a critical role in adipogenic differentiation of preadipocytes. Gain-of-function and loss-of-function studies revealed that E4BP4 acts as a positive regulator of adipogenesis in 3T3-L1 cells. E4BP4 was markedly induced by glucocorticoid (dexamethasone) via GR and cAMP response element-binding protein (CREB) during adipogenesis...
April 14, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28414132/epigenetic-modification-of-glucocorticoid-receptor-promoter-i7-in-maternally-separated-and-restraint-stressed-rats
#8
Sung Woo Park, Jung Goo Lee, Mi Kyoung Seo, Nguyen Ngoc Ly, Chan Hong Lee, Hye Yeon Cho, Le Thi Hein, Ah Jeong Choi, Gyung-Mee Kim, Young Hoon Kim
Glucocorticoid receptor (GR) promoter I7 is susceptible to epigenetic changes induced by environmental influences. Early life stress (ELS) has a persistent impact on GR expression, as well as behavior, in adult rodents via epigenetic changes of GR promoter I7. Moreover, various stressors can induce histone modifications in this region during adulthood. Thus, the present study aimed to investigate whether maternally separated (MS) rats exposed to chronic restraint stress (RS) would exhibit histone modifications of GR promoter I7 in the hippocampus...
April 13, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28413431/asian-house-rats-may-facilitate-their-invasive-success-through-suppressing-brown-rats-in-chronic-interaction
#9
Hong-Ling Guo, Hua-Jing Teng, Jin-Hua Zhang, Jian-Xu Zhang, Yao-Hua Zhang
BACKGROUND: The Asian house rat (Rattus tanezumi) and the brown rat (Rattus norvegicus) are closely related species and are partially sympatric in southern China. Over the past 20 years, R. tanezumi has significantly expanded northward in China and partially replaced the native brown rat subspecies, R. n. humiliatus. Although invasive species are often more aggressive than native species, we did not observe interspecific physical aggression between R. tanezumi and R. n. humiliatus. Here, we focused on whether or not R...
2017: Frontiers in Zoology
https://www.readbyqxmd.com/read/28408351/inhibition-of-heat-shock-protein-90-rescues-glucocorticoid-induced-bone-loss-through-enhancing-bone-formation
#10
Haixiao Chen, Ji Xing, Xinhua Hu, Lihua Chen, Haiyan Lv, Chengyun Xu, Dun Hong, Ximei Wu
Endogenous glucocorticoids (GCs) support normal bone development and bone mass maintenance, whereas long-term exposure to pharmacological dosages of GCs uncouples bone formation and resorption, resulting in GC-induced osteoporosis (GIOP). Heat shock protein 90 (HSP90) chaperoning glucocorticoid receptor (GR) signaling prompts us to speculate that HSP90 plays critical roles in GC-mediated bone formation and GIOP. In the present study, inhibition of HSP90 activity by 17-Demethoxy-17-allyaminogeldanmycin (17-AAG) or knockdown of HSP90 expression by siRNAs attenuated dexamethasone(Dex)-induced GR nuclear accumulation and transcriptional output of GR signaling, whereas overexpression of HSP90α or HSP90β enhanced GR transactivity in C3H10T1/2 cells...
April 10, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28408299/ovarian-hormones-modify-anxiety-behavior-and-glucocorticoid-receptors-after-chronic-social-isolation-stress
#11
Dinah L Ramos-Ortolaza, Raura J Doreste-Mendez, John K Alvarado-Torres, Annelyn Torres-Reveron
Chronic social isolation could lead to a disruption in the Hypothalamic-Pituitary-Adrenal (HPA) axis, resulting in anxiety and depressive-like behaviors but cycling estrogens could modify these behaviors. The aim of this study was to determine if changes in ovarian hormones during the normal cycle could interact with social isolation to alter anxiety and depressive-like behaviors. In parallel, we examined the expression of glucocorticoid receptor (GR) and synaptic vesicle protein synaptophysin in the hippocampus and hypothalamus of Sprague Dawley normal cycling female rats...
April 10, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28403881/glucocorticoid-receptor-represses-brain-derived-neurotrophic-factor-expression-in-neuron-like-cells
#12
Hui Chen, Marc Lombès, Damien Le Menuet
Brain-derived neurotrophic factor (BDNF) is involved in many functions such as neuronal growth, survival, synaptic plasticity and memorization. Altered expression levels are associated with many pathological situations such as depression, epilepsy, Alzheimer's, Huntington's and Parkinson's diseases. Glucocorticoid receptor (GR) is also crucial for neuron functions, via binding of glucocorticoid hormones (GCs). GR actions largely overlap those of BDNF. It has been proposed that GR could be a regulator of BDNF expression, however the molecular mechanisms involved have not been clearly defined yet...
April 12, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28402861/trpv1-regulates-stress-responses-through-hdac2
#13
Sung Eun Wang, Seung Yeon Ko, Sungsin Jo, Miyeon Choi, Seung Hoon Lee, Hye-Ryeong Jo, Jee Young Seo, Sang Hoon Lee, Yong-Seok Kim, Sung Jun Jung, Hyeon Son
Stress causes changes in neurotransmission in the brain, thereby influencing stress-induced behaviors. However, it is unclear how neurotransmission systems orchestrate stress responses at the molecular and cellular levels. Transient receptor potential vanilloid 1 (TRPV1), a non-selective cation channel involved mainly in pain sensation, affects mood and neuroplasticity in the brain, where its role is poorly understood. Here, we show that Trpv1-deficient (Trpv1(-/-)) mice are more stress resilient than control mice after chronic unpredictable stress...
April 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28401766/occurrence-and-in-vitro-bioactivity-of-estrogen-androgen-and-glucocorticoid-compounds-in-a-nationwide-screen-of-united-states-stream-waters
#14
Justin M Conley, Nicola Evans, Mary C Cardon, Laura Rosenblum, Luke R Iwanowicz, Phillip C Hartig, Kathleen M Schenck, Paul M Bradley, Vickie S Wilson
In vitro bioassays are sensitive, effect-based tools used to quantitatively screen for chemicals with nuclear receptor activity in environmental samples. We measured in vitro estrogen (ER), androgen (AR), and glucocorticoid receptor (GR) activity, along with a broad suite of chemical analytes, in streamwater from 35 well-characterized sites (3 reference and 32 impacted) across 24 states and Puerto Rico. ER agonism was the most frequently detected with nearly all sites (34/35) displaying activity (range, 0.054-116 ng E2Eq L(-1))...
April 12, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28400302/decreased-comfort-food-intake-and-allostatic-load-in-adolescents-carrying-the-a3669g-variant-of-the-glucocorticoid-receptor-gene
#15
Danitsa Marcos Rodrigues, Roberta Sena Reis, Roberta Dalle Molle, Tania Diniz Machado, Amanda Brondani Mucellini, Andressa Bortoluzzi, Rudineia Toazza, Juliano Adams Pérez, Giovanni Abrahão Salum, Marilyn Agranonik, Luciano Minuzzi, Robert D Levitan, Augusto Buchweitz, Alexandre Rosa Franco, Gisele Gus Manfro, Patrícia Pelufo Silveira
BACKGROUND: The A3669G single nucleotide polymorphism (SNP) of the glucocorticoid receptor (GR) gene NR3C1 is associated with altered tissue sensitivity to glucocorticoids (GCs). GCs modulate the food reward circuitry and are implicated in increased intake of palatable foods, which can lead to the metabolic syndrome and obesity. We hypothesized that presence of the G variant of the A3669G SNP would affect preferences for palatable foods and alter metabolic, behavioural, and neural outcomes...
April 8, 2017: Appetite
https://www.readbyqxmd.com/read/28397446/glucocorticoid-receptor-polymorphism-in-obesity-and-glucose-homeostasis
#16
REVIEW
Agnieszka Majer-Łobodzińska, Joanna Adamiec-Mroczek
Glucocorticoid receptor (GR) activity plays a significant role in the etiology of obesity and is essential for glucose homeostasis, the development of hyperinsulinaemia and subsequent increased fat deposition. Several polymorphisms in the GR gene have been described, and at least three of them seem to be associated with altered glucocorticoid sensitivity and changes in glucose homeostasis, and other metabolic parameters. The N363S polymorphism has been associated with increased sensitivity to glucocorticoides, increased insulin response to dexamethasone and increased plasma glucose level...
January 2017: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/28396564/structural-analysis-of-the-glucocorticoid-receptor-ligand-binding-domain-in-complex-with-triamcinolone-acetonide-and-a-fragment-of-the-atypical-coregulator-shp
#17
Emily R Weikum, Denise C Okafor, Emma H D'Agostino, Jennifer K Colucci, Eric A Ortlund
The synthetic glucocorticoids (GCs) dexamethasone, mometasone furoate, and triamcinolone acetonide have been pharmaceutical mainstays to treat chronic inflammatory diseases. These drugs bind to the glucocorticoid receptor (GR), a ligand- activated transcription factor and member of the nuclear receptor superfamily. GR is widely recognized as a therapeutic target for its ability to counter pro-inflammatory signaling. Despite the popularity of GCs in the clinic, long-term use leads to numerous side effects, driving the need for new and improved drugs with less off-target pharmacology...
April 10, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28381557/glucocorticoid-receptor-binding-to-chromatin-is-selectively-controlled-by-coregulator-hic-5-and-chromatin-remodeling-enzymes
#18
Brian H Lee, Michael R Stallcup
The steroid hormone-activated glucocorticoid receptor (GR) regulates cellular stress pathways by binding to genomic regulatory elements of target genes and recruiting coregulator proteins to remodel chromatin and regulate transcription complex assembly. The coregulator Hydrogen peroxide-inducible clone 5 (Hic-5) is required for glucocorticoid (GC) regulation of some genes, but not others, and blocks regulation of a third gene set by inhibiting GR binding. How Hic-5 exerts these gene-specific effects, and specifically how it blocks GR binding to some genes but not others is unclear...
April 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28375666/glucocorticoid-receptor-chip-seq-identifies-plcd1-as-a-klf15-target-that-represses-airway-smooth-muscle-hypertrophy
#19
Sarah K Sasse, Vineela Kadiyala, Thomas Danhorn, Reynold A Panettieri, Tzu L Phang, Anthony N Gerber
Glucocorticoids exert important therapeutic effects on airway smooth muscle (ASM), yet few direct targets of glucocorticoid signaling in ASM have been definitively identified. Here, we show that the transcription factor, KLF15, is directly induced by glucocorticoids in primary human ASM and that KLF15 represses ASM hypertrophy. We integrated transcriptome data from KLF15 overexpression with genome-wide analysis of RNA Polymerase II (RNAPII) and glucocorticoid receptor (GR) occupancy (i.e. ChIP-seq) to identify PLCD1 as both a KLF15-regulated gene and a novel repressor of ASM hypertrophy...
April 4, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28374517/striae-distensae-immunohistochemical-assessment-of-hormone-receptors-in-multigravida-and-nulligravida
#20
Sahar El Sayed Youssef, Ekramy Ahmed El-Khateeb, Dalia Gamal Aly, Manal Hassan Moussa
BACKGROUND: Striae distensae (SD), a type of dermal scarring, are psychologically disappointing. To date, information and scientific research behind the role of hormonal factors in the development of SD are still unclear. It is vital to understand striae to offer patients the best therapeutic options. OBJECTIVES: To investigate early alterations regarding the expression of estrogen, androgen, and glucocorticoid receptors (estrogen receptor (ER), androgen receptor (AR), glucocorticoid receptor (GR) in skin samples of multigravida (MG) and nulligravida (NG) cases and to compare them with normal controls...
April 4, 2017: Journal of Cosmetic Dermatology
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