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Glucocorticoid receptor ( GR )

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https://www.readbyqxmd.com/read/29223294/glucocorticoid-hormone-treatment-enhances-the-cytokine-production-of-regulatory-t-cells-by-upregulation-of-foxp3-expression
#1
Emese Ugor, Lilla Prenek, Ramóna Pap, Gergely Berta, Dávid Ernszt, József Najbauer, Péter Németh, Ferenc Boldizsár, Tímea Berki
OBJECTIVE: Despite the fact that glucocorticoids (GC) are important therapeutic tools, their effects on regulatory T cells (Treg) are not well defined. The aim of our work was to investigate how GCs influence in vivo the thymic (tTreg) and peripheral Treg (pTreg) differentiation, survival and cytokine production. METHODS: Tregs were detected with flow cytometry in lymphatic organs of 4-6 weeks old BALB/c mice after repeated (2-4days), high-dose in vivo GC treatment using CD4/CD25 cell surface and Foxp3/IL-10/TGFβ/glucocorticoid receptor (GR) intracellular staining...
October 6, 2017: Immunobiology
https://www.readbyqxmd.com/read/29223280/circadian-and-ultradian-patterns-of-hpa-axis-activity-in-rodents-significance-for-brain-functionality
#2
REVIEW
Femke S den Boon, R Angela Sarabdjitsingh
The hypothalamo-pituitary-adrenal (HPA) axis comprises interactions between the hypothalamus, the pituitary and the adrenal glands and its activation results in the release of corticosteroid hormones. Corticosteroids are secreted from the adrenal gland in a distinct 24-h circadian rhythm overarching an ultradian rhythm, which consists of hourly corticosteroid pulses exposing target tissues to rapidly changing steroid levels. On top of these rhythms surges can take place after stress. HPA-axis rhythms promote adaptation to predictable (i...
October 2017: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29222744/activation-of-intestinal-gr-fxr-and-ppar%C3%AE-ugt-signaling-exacerbates-ibuprofen-induced-enteropathy-in-mice
#3
Zhiqiang Lu, Yuanfu Lu, Xue Wang, Fangyu Wang, Youcai Zhang
Nonsteroidal anti-inflammatory drugs (NSAIDs)-induced small intestinal injury (enteropathy) occurs in about two-thirds of regular NSAID users. To date, there is no proven-effective treatment for NSAID enteropathy, and its underlying mechanism remains obscure. The present study showed that glucocorticoids are an important determinant of NSAID enteropathy. High dose dexamethasone (DEX, 75 mg/kg) markedly exacerbated the acute toxicity of ibuprofen (IBU, 200 mg/kg) in the small intestine of mice, which was not due to the pregnane-X-receptor pathway...
December 8, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29217668/induced-global-deletion-of-glucocorticoid-receptor-impairs-fracture-healing
#4
Anna E Rapp, Yasmine Hachemi, Julia Kemmler, Mascha Koenen, Jan Tuckermann, Anita Ignatius
Although endogenous glucocorticoids (GCs) are important regulators of bone integrity and the immune system, their role in bone repair after fracture-a process highly dependent on inflammation and bone formation-is unclear. Because most effects of GCs are mediated by the glucocorticoid receptor (GR), we used an inducible global GR knockout (GRgtROSACreERT2) mouse model to eliminate endogenous GC action in all cells contributing to bone repair. The healing process was analyzed by cytokine/chemokine multiplex analysis, flow cytometry, histology, gene-expression analysis, microcomputed tomography, and biomechanical analysis...
December 7, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29206196/the-fkbp51-glucocorticoid-receptor-co-chaperone-regulation-function-and-implications-in-health-and-disease
#5
REVIEW
Gabriel R Fries, Nils C Gassen, Theo Rein
Among the chaperones and co-chaperones regulating the glucocorticoid receptor (GR), FK506 binding protein (FKBP) 51 is the most intensely investigated across different disciplines. This review provides an update on the role of the different co-chaperones of Hsp70 and Hsp90 in the regulation of GR function. The development leading to the focus on FKBP51 is outlined. Further, a survey of the vast literature on the mechanism and function of FKBP51 is provided. This includes its structure and biochemical function, its regulation on different levels-transcription, post-transcription, and post-translation-and its function in signaling pathways...
December 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29203717/hsp90-and-fkbp51-complex-regulators-of-psychiatric-diseases
#6
REVIEW
Marangelie Criado-Marrero, Theo Rein, Elisabeth B Binder, James T Porter, John Koren, Laura J Blair
Mood disorders affect nearly a quarter of the world's population. Therefore, understanding the molecular mechanisms underlying these conditions is of great importance. FK-506 binding protein 5 (FKBP5) encodes the FKBP51 protein, a heat shock protein 90 kDa (Hsp90) co-chaperone, and is a risk factor for several affective disorders. FKBP51, in coordination with Hsp90, regulates glucocorticoid receptor (GR) activity via a short negative feedback loop. This signalling pathway rapidly restores homeostasis in the hypothalamic-pituitary-adrenal (HPA) axis following stress...
January 19, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29196557/selexglm-differentiates-androgen-and-glucocorticoid-receptor-dna-binding-preference-over-an-extended-binding-site
#7
Liyang Zhang, Gabriella D Martini, H Tomas Rube, Judith F Kribelbauer, Chaitanya Rastogi, Vincent D FitzPatrick, Jon C Houtman, Harmen J Bussemaker, Miles A Pufall
The DNA-binding interfaces of the androgen (AR) and glucocorticoid (GR) receptors are virtually identical, yet these transcription factors share only about a third of their genomic binding sites and regulate similarly distinct sets of target genes. To address this paradox, we determined the intrinsic specificities of the AR and GR DNA binding domains using a refined version of SELEX-seq. We developed an algorithm, SelexGLM, that quantifies binding specificity over a large (31 bp) binding-site by iteratively fitting a feature-based generalized linear model to SELEX probe counts...
December 1, 2017: Genome Research
https://www.readbyqxmd.com/read/29196164/glucocorticoids-indirectly-decrease-colon-cancer-cell-proliferation-and-invasion-via-effects-on-cancer-associated-fibroblasts
#8
Zuzanna Drebert, Elly De Vlieghere, Jolien Bridelance, Olivier De Wever, Karolien De Bosscher, Marc Bracke, Ilse M Beck
Cancer-associated fibroblasts (CAFs) support cancer growth, invasion, and metastasis. Glucocorticoids (GCs), drugs often administered together with chemotherapy, are steroidal ligands of the glucocorticoid receptor (GR), a transcription factor which upon activation regulates expression of multiple genes involved in suppression of inflammation. We have previously shown that in dexamethasone (Dex)-treated CAFs derived from colon cancer, production and secretion of several factors related to cancer progression, such as tenascin C (TNC) and hepatocyte growth factor (HGF), were strongly suppressed...
November 28, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29196049/chronic-glucocorticoid-treatment-induced-circadian-clock-disorder-leads-to-lipid-metabolism-and-gut-microbiota-alterations-in-rats
#9
Tao Wu, Luna Yang, Jianguo Jiang, Yinhua Ni, Jiawei Zhu, Xiaojun Zheng, Qi Wang, Xin Lu, Zhengwei Fu
AIM: Glucocorticoids (GCs), steroid hormones synthetized by the adrenal gland, are regulated by circadian cycles, and dysregulation of GC signaling can lead to the development of metabolic syndrome. The effects and potential mechanism of GCs in physiology were investigated in the present study. MAIN METHODS: Male Wistar rats were orally administered dexamethasone sodium phosphate (DEX, 0.01 and 0.05mg/kg body weight per day) for 7weeks. KEY FINDING: DEX treatment attenuated body weight gain and reduced food intake, whereas it induced the accumulation of fat...
November 28, 2017: Life Sciences
https://www.readbyqxmd.com/read/29194690/a-carbon-21-steroidal-metabolite-from-progestin-20%C3%AE-hydroxy-5%C3%AE-dihydroprogesterone-stimulates-the-androgen-receptor-in-prostate-cancer-cells
#10
Takashi Ando, Tsutomu Nishiyama, Itsuhiro Takizawa, Yoshimichi Miyashiro, Noboru Hara, Yoshihiko Tomita
BACKGROUND: Clarifying the mechanisms underlying prostate cancer (PC) progression and resistance to androgen deprivation therapy (ADT) is an urgent clinical issue. ADT influences steroidal metabolism in patients with PC and promotes the accumulation of carbon 21 steroids (C21s), such as progestin. Because the enzymes responsible for C21s metabolism are similar to those for androgen metabolism, PC cells may be able to metabolize C21s intracellularly. Therefore, there is a possibility that intracrine C21s are implicated in PC progression and resistance to ADT, and the influence of C21s on PC cells is yet to be elucidated...
December 1, 2017: Prostate
https://www.readbyqxmd.com/read/29189098/the-effects-of-ovarian-hormones-on-stressor-induced-hormonal-responses-glucocorticoid-receptor-expression-and-translocation-and-genes-related-to-receptor-signaling-in-adult-female-rats
#11
Matthew R Green, Marina L Marcolin, Cheryl M McCormick
Estradiol potentiates hypothalamic-pituitary-adrenal activity and delays the return of glucocorticoid secretion to baseline after a stressor exposure in female rats; we investigated whether estradiol effects involve actions on glucocorticoid receptor (GR) translocation and expression of receptor co-chaperones. In Experiment 1 intact females and ovariectomized (OVX) females were treated for four days with vehicle (VEH), 17β-estradiol benzoate (EB), or EB and progesterone (EB + P). Samples were taken from rats in the home cage (baseline) or after 30 min of restraint stress in a plastic restrainer (post-restraint) (n = 10/group)...
November 30, 2017: Stress: the International Journal on the Biology of Stress
https://www.readbyqxmd.com/read/29182159/epigenetic-changes-of-fkbp5-as-a-link-connecting-genetic-and-environmental-risk-factors-with-structural-and-functional-brain-changes-in-major-depression
#12
Leonardo Tozzi, Chloe Farrell, Linda Booij, Kelly Doolin, Zsofia Nemoda, Moshe Szyf, Florence B Pomares, Julian Chiarella, Veronica O'Keane, Thomas Frodl
The gene for the glucocorticoid receptor regulator FK506 binding protein 5 (FKBP5) plays a role for risk, response to treatment and changes in brain areas in major depressive disorder (MDD). Chronic stress is associated with lower methylation of FKBP5. Our aim was to investigate whether methylation of FKBP5 reflected exposure to childhood adversity in MDD and controls and whether it was associated with structure and function of emotional processing regions. FKBP5 intron 7 GR response element region methylation and rs1360780 allelic status were assessed from whole blood in 56 MDD adults and 50 controls...
November 28, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29175389/repetitive-restraint-stress-changes-spleen-immune-cell-subsets-through-glucocorticoid-receptor-or-%C3%AE-adrenergic-receptor-in-a-stage-dependent-manner
#13
Yu Li, Wei Jiang, Zhen-Zhen Li, Chen Zhang, Chen Huang, Jun Yang, Guang-Yao Kong, Zong-Fang Li
Immune system is sensitive to stress. Spleen is the largest peripheral immune organ innervated with sympathetic nerves and controlled by adrenomedullary system in the body. However, the alterations and mechanism of spleen immune cell subsets caused by repetitive restraint stress (RRS) is poorly understood. In this study, we found that RRS reduced spleen index in mice, and induced an expansion of white pulp and involution of the red pulp. Meanwhile, the percentage of CD3+CD8+ T lymphocytes, CD11b+F4/80+ macrophages, CD11b+Ly-6G-Ly-6Chi monocytic myeloid derived suppressor cells (mMDSCs) and CD11b+Ly-6G+Ly-6Cint granulocytic myeloid derived suppressor cells (gMDSCs) in spleen were significantly changed by RRS...
November 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29175245/characterization-of-two-channel-catfish-ictalurus-punctatus-glucocorticoid-receptors-and-expression-following-an-acute-stressor
#14
Brian C Small, Sylvie M A Quiniou
Two channel catfish glucocorticoid receptor genes, ipGR1 (NR3C1_1) and ipGR2 (NR3C1_2) were partially characterized. Identification and analysis of the genomic organization of two channel catfish glucocorticoid (GC) receptors (GRs) revealed differences in the lengths of exons 1 and 2 and the addition of an extra 27-bp exon inserted after exon 2 in the GR1 gene, yielding a 9-aa insert in the receptor protein. Sequence of the 9-aa insert in ipGR1 (WRARQNTHG) is unique compared to other teleost fish GRs. Amino acid sequence alignment of the two channel catfish GRs, revealed 55% sequence identity between them, with a high degree of sequence conservation (82%) in the DNA binding and ligand binding domains...
November 22, 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/29174640/dorsal-raph%C3%A3-nucleus-glucocorticoid-receptors-inhibit-tph2-gene-expression-in-male-c57bl-6j-mice
#15
Melanie Y Vincent, Nina C Donner, David G Smith, Christopher A Lowry, Lauren Jacobson
The serotonergic dorsal raphé nucleus (DRN) expresses glucocorticoid receptors (GR), and systemic glucocorticoids have been shown to regulate expression and activity of tryptophan hydroxylase isoform 2, the rate-limiting enzyme for serotonin synthesis in brain. We have used intra-DRN injection of pseudotyped adeno-associated virus AAV2/9 transducing either green fluorescent protein (GFP control) or Cre recombinase (DRN GR deletion) in floxed GR mice to determine if DRN GR directly regulate DRN mRNA levels of tryptophan hydroxylase 2 (tph2)...
November 22, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29170386/glucocorticoid-induced-phosphorylation-by-cdk9-modulates-the-coactivator-functions-of-transcriptional-cofactor-grip1-in-macrophages
#16
David A Rollins, Joubert B Kharlyngdoh, Maddalena Coppo, Bowranigan Tharmalingam, Sanda Mimouna, Ziyi Guo, Maria A Sacta, Miles A Pufall, Robert P Fisher, Xiaoyu Hu, Yurii Chinenov, Inez Rogatsky
The glucocorticoid (GC) receptor (GR) suppresses inflammation by activating anti-inflammatory and repressing pro-inflammatory genes. GR-interacting protein-1 (GRIP1) is a GR corepressor in macrophages, however, whether GRIP1 mediates GR-activated transcription, and what dictates its coactivator versus corepressor properties is unknown. Here we report that GRIP1 loss in macrophages attenuates glucocorticoid induction of several anti-inflammatory targets, and that GC treatment of quiescent macrophages globally directs GRIP1 toward GR binding sites dominated by palindromic GC response elements (GRE), suggesting a non-redundant GRIP1 function as a GR coactivator...
November 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/29167235/cortisol-limits-selected-actions-of-synthetic-glucocorticoids-in-the-airway-epithelium
#17
Danica Prodanovic, Christine R Keenan, Shenna Langenbach, Meina Li, Qianyu Chen, Michael J Lew, Alastair G Stewart
Cortisol, a physiologic glucocorticoid (GC), is essential for growth and differentiation of the airway epithelium. Epithelial function influences inflammation in chronic respiratory diseases. Synthetic GCs, including inhaled corticosteroids, exert anti-inflammatory effects in airway epithelium by transactivation of genes and by inhibition of proinflammatory cytokine release. We examined the effect of cortisol on the actions of synthetic GCs in the airway epithelium, demonstrating that cortisol acts like a partial agonist at the GC receptor (GR), limiting GC-induced GR-dependent transcription in the BEAS-2B human bronchial epithelial cell line...
November 22, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29163473/treadmill-slope-modulates-inflammation-fiber-type-composition-androgen-and-glucocorticoid-receptors-in-the-skeletal-muscle-of-overtrained-mice
#18
Alisson L da Rocha, Bruno C Pereira, Giovana R Teixeira, Ana P Pinto, Fabiani G Frantz, Lucila L K Elias, Fábio S Lira, José R Pauli, Dennys E Cintra, Eduardo R Ropelle, Leandro P de Moura, Rania A Mekary, Ellen C de Freitas, Adelino S R da Silva
Overtraining (OT) may be defined as an imbalance between excessive training and adequate recovery period. Recently, a downhill running-based overtraining (OTR/down) protocol induced the nonfunctional overreaching state, which is defined as a performance decrement that may be associated with psychological and hormonal disruptions and promoted intramuscular and systemic inflammation. To discriminate the eccentric contraction effects on interleukin 1beta (IL-1β), IL-6, IL-10, IL-15, and SOCS-3, we compared the release of these cytokines in OTR/down with other two OT protocols with the same external load (i...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163463/selective-glucocorticoid-receptor-properties-of-gsk866-analogs-with-cysteine-reactive-warheads
#19
Chandra S Chirumamilla, Ajay Palagani, Balu Kamaraj, Ken Declerck, Marinus W C Verbeek, Ryabtsova Oksana, Karolien De Bosscher, Nadia Bougarne, Bart Ruttens, Kris Gevaert, René Houtman, Winnok H De Vos, Jurgen Joossens, Pieter Van Der Veken, Koen Augustyns, Xaveer Van Ostade, Annemie Bogaerts, Hans De Winter, Wim Vanden Berghe
Synthetic glucocorticoids (GC) are the mainstay therapy for treatment of acute and chronic inflammatory disorders. Due to the high adverse effects associated with long-term use, GC pharmacology has focused since the nineties on more selective GC ligand-binding strategies, classified as selective glucocorticoid receptor (GR) agonists (SEGRAs) or selective glucocorticoid receptor modulators (SEGRMs). In the current study, GSK866 analogs with electrophilic covalent-binding warheads were developed with potential SEGRA properties to improve their clinical safety profile for long-lasting topical skin disease applications...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29162310/therapeutic-mechanisms-of-glucocorticoids
#20
REVIEW
Jolien Vandewalle, Astrid Luypaert, Karolien De Bosscher, Claude Libert
Glucocorticoids (GCs) have been used clinically for decades as potent anti-inflammatory and immunosuppressive agents. Nevertheless, their use is severely hampered by the risk of developing side effects and the occurrence of glucocorticoid resistance (GCR). Therefore, efforts to understand the complex mechanisms underlying GC function and GCR are ongoing. The goal is to generate new glucocorticoid receptor (GR) ligands that can dissociate anti-inflammatory from metabolic side effects and/or overcome GCR. In this review paper we discuss recent insights into GR-mediated actions in GCR and novel therapeutic strategies for acute and chronic inflammatory diseases...
November 18, 2017: Trends in Endocrinology and Metabolism: TEM
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