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Glucocorticoid receptor

Yun Hu, Qinwei Sun, Yan Hu, Zhen Hou, Yibo Zong, Nagmeldin A Omer, Halima Abobaker, Ruqian Zhao
Background: We have shown previously that in ovo betaine injection can prevent nonalcoholic fatty liver induced by glucocorticoid exposure in chickens; yet it remains unknown whether feeding betaine to laying hens may exert similar effects in their progeny. Objective: In this study, we fed laying hens a betaine-supplemented diet, and the progeny were later exposed chronically to corticosterone (CORT) to test hepatoprotective effects and further elucidate underlying mechanisms...
March 1, 2018: Journal of Nutrition
Yong-Jun Xu, Hui Sheng, Tian-Wen Wu, Qing-Yue Bao, You Zheng, Yan-Min Zhang, Yu-Xiang Gong, Jian-Qiang Lu, Zhen-Dong You, Yang Xia, Xin Ni
Pregnant women at risk of preterm labor usually receive synthetic glucocorticoids (sGCs) to promote fetal lung development. Emerging evidence indicates that antenatal sGC increases the risk of affective disorders in offspring. Data from animal studies show that such disorders can be transmitted to the second generation. However, the molecular mechanisms underlying the intergenerational effects of prenatal sGC remain largely unknown. Here we show that prenatal dexamethasone (Dex) administration in late pregnancy induced depression-like behavior in first-generation (F1) offspring, which could be transmitted to second-generation (F2) offspring with maternal dependence...
March 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Hong-Ren Yu, You-Lin Tain, Mao-Meng Tiao, Chih-Cheng Chen, Jiunn-Ming Sheen, I-Chun Lin, Shih-Wen Li, Ching-Chou Tsai, Yu-Ju Lin, Kai-Sheng Hsieh, Li-Tung Huang
BACKGROUND: Hypertension may result from high-fat (HF) diet induced-obesity and overexposure to glucocorticoids in utero. Recent studies demonstrated the potent contribution of adipose tissue's renin-angiotensin system (RAS) to systemic RAS, which plays a key role in regulating blood pressure (BP). In this study, we investigated the effects of prenatal dexamethasone (DEX) exposure and postnatal HF diet on RAS of adipose tissue. METHODS: RAS and BP of 6-month old rats exposed to prenatal DEX and/or postnatal HF diet were examined...
March 14, 2018: Lipids in Health and Disease
Jeffery M Vahrenkamp, Chieh-Hsiang Yang, Adriana C Rodriguez, Aliyah Almomen, Kristofer C Berrett, Alexis N Trujillo, Katrin P Guillen, Bryan E Welm, Elke A Jarboe, Margit M Janat-Amsbury, Jason Gertz
Steroid hormone receptors are simultaneously active in many tissues and are capable of altering each other's function. Estrogen receptor α (ER) and glucocorticoid receptor (GR) are expressed in the uterus, and their ligands have opposing effects on uterine growth. In endometrial tumors with high ER expression, we surprisingly found that expression of GR is associated with poor prognosis. Dexamethasone reduced normal uterine growth in vivo; however, this growth inhibition was abolished in estrogen-induced endometrial hyperplasia...
March 13, 2018: Cell Reports
Yanhua Hu, Julie A Carman, Deborah Holloway, Selena Kansal, Li Fan, Christine Goldstine, Deborah Lee, John E Somerville, Robert Latek, Robert Townsend, Alyssa Johnsen, Sean Connolly, Somnath Bandyopadhyay, Nancy Shadick, Michael E Weinblatt, Richard Furie, Steven G Nadler
OBJECTIVE: To develop an objective, readily measurable pharmacodynamic biomarker of glucocorticoid (GC) activity. METHODS: Genes modulated by prednisolone were identified from in vitro studies using peripheral blood mononuclear cells from normal healthy volunteers (NHVs). Using the criteria of a >2-fold change relative to vehicle controls and an adjusted P value cutoff of <0.05, 64 upregulated and 18 downregulated genes were identified. A composite score of the upregulated genes was generated using a single-sample gene set enrichment analysis algorithm...
March 13, 2018: Arthritis & Rheumatology
Maria Maiarù, Oakley B Morgan, Tianqi Mao, Michaela Breitsamer, Harry Bamber, Max Pöhlmann, Mathias V Schmidt, Gerhard Winter, Felix Hausch, Sandrine M Géranton
It is well-established that FKBP51 regulates the stress system by modulating the sensitivity of the glucocorticoid receptor to stress hormones. Recently, we have demonstrated that FKBP51 also drives long-term inflammatory pain states in male mice by modulating glucocorticoid-signalling at spinal cord level. Here, we explored the potential of FKBP51 as a new pharmacological target for the treatment of persistent pain across the sexes. First, we demonstrated that FKBP51 regulates long-term pain states of different aetiologies independently of sex...
March 12, 2018: Pain
Sisi Gao, Pierre J Deviche
Stress-induced inhibition of innate immune activity is widespread in free-ranging birds, but the mechanisms that are responsible for this inhibition are poorly understood. We previously demonstrated that an increase in plasma corticosterone (CORT), the primary avian glucocorticoid, is necessary for the inhibition of natural antibody- and complement-mediated as well as bactericidal activities to occur during stress. Here we investigated the role of glucocorticoid receptors in stress-induced inhibition of natural antibody- and complement-mediated activities and bactericidal activity within non-genomic (<10 min) and genomic (<120 min) time frames in male House Sparrows, Passer domesticus...
March 9, 2018: Developmental and Comparative Immunology
Allison K Farrell, Richard B Slatcher, Erin T Tobin, Ledina Imami, Derek E Wildman, Francesca Luca, Samuele Zilioli
The glucocorticoid receptor gene NR3C1 is an important down-regulator of inflammation and is typically under-expressed in individuals with low socioeconomic status (SES). Negative emotionality has been suggested as a potential mediator of SES disparities in health outcomes. In this study, we expand this literature by naturalistically assessing negative emotionality in a key emotional environment: the family. In a sample of 104 youth with asthma (10-17 years) and their primary caregiver, we assessed SES via caregiver report, emotional expression by youth and parents in the home over four days using the electronically activated recorder (EAR), and NR3C1 expression via blood collected from youth...
February 15, 2018: Psychoneuroendocrinology
Xiao-Xiao Ma, Jin Liu, Chun-Man Wang, Jiang-Ping Zhou, Zhen-Zhou He, Han Lin
AIMS: This study was to determine whether curcumin had any effect on the proliferation of neural stem cell (NSC), analyze the expression of glucocorticoid receptor (GR), signal transducer and activator of transcription 3 (STAT3), and Notch1 at transcription and protein level, and discuss the related mechanisms. METHODS AND RESULTS: NSCs were harvested from E15 SD rat brain and cultured. All experiments were performed at the second passage. Cell cytotoxicity, cell viability, and proliferation assays were used to figure out the optimal concentration of curcumin, which can be used for the protein and mRNA studies...
March 12, 2018: CNS Neuroscience & Therapeutics
Ying Huang, Gui-Quan Cai, Jian-Ping Peng, Chao Shen
Based on the results from our previous study, dexamethasone (Dex) increases reactive oxygen species (ROS) levels and subsequently induces cell death and matrix catabolism in chondrocytes. Nevertheless, the mechanism underlying this phenomenon remains unclear. Nicotinamide adenine dinucleotide (phosphate) (NADPH) oxidase 4 (NOX4) is one of the major enzymes responsible for intracellular ROS production during the inflammatory process. The objective of the current study was to investigate the role of NOX4 in Dex-induced ROS over-production...
March 8, 2018: Journal of Steroid Biochemistry and Molecular Biology
Cristian Herrera, Miguel Marcos, Cristina Carbonell, José Antonio Mirón-Canelo, Gerard Espinosa, Ricard Cervera, Antonio-Javier Chamorro
INTRODUCTION: The human glucocorticoid receptor gene (NR3C1) is considered to play a role in the differences and sensitivities of the glucocorticoid response in individuals with autoimmune diseases. The objective of this study was to examine by means of a systematic review previous findings regarding allelic variants of NR3C1 in relation to the risk of developing systemic autoimmune diseases. METHODS: Studies that analysed the genotype distribution of NR3C1 allelic variants among patients with systemic autoimmune diseases were retrieved...
March 8, 2018: Autoimmunity Reviews
Alessia Para, Ying Li, Gloria M Coruzzi
Chromatin immunoprecipitation (ChIP) is a widely used method to map the position of DNA-binding proteins such as histones and transcription factors (TFs) upon their interaction with particular regions of the genome. To examine the genomic distribution of a TF in specific cell types in response to a change in nitrogen concentration, we developed a micro-ChIP (μChIP) protocol that requires only ~5000 Arabidopsis cells transiently expressing the Arabidopsis TF Basic Leucine Zipper 1 (bZIP1) fused to the glucocorticoid receptor (GR) domain that mediates nuclear import in the presence of dexamethasone...
2018: Methods in Molecular Biology
Eric P Hoffman, Valerie Riddle, Maxime A Siegler, Daniel Dickerson, Miroslav Backonja, William G Kramer, Kanneboyina Nagaraju, Heather Gordish-Dressman, Jesse M Damsker, John M McCall
BACKGROUND: Glucocorticoid drugs are highly effective anti-inflammatory agents, but chronic use is associated with extensive pharmacodynamic safety concerns that have a considerable negative impact on patient quality of life. PURPOSE: Vamorolone (VBP15) is a first-in-class steroidal multi-functional drug that shows potent inhibition of pro-inflammatory NFkB pathways via high-affinity binding to the glucocorticoid receptor, high affinity antagonism for the mineralocorticoid receptor, and membrane stabilization properties...
March 7, 2018: Steroids
Anna Kurek, Katarzyna Głombik, Jan Detka, Agnieszka Basta-Kaim, Marta Kubera, Władysław Lasoń, Bogusława Budziszewska
Obesity is a disease that often co-occurs with depression, and some evidence indicates that chronic stress in the perinatal period, in association with overactive glucocorticoids, can cause permanent changes that increase the risk of the development of both depression and obesity later in life. However, the mechanism responsible for the overly potent action of glucocorticoids in both depression and obesity is not known. The aim of the present study was to determine the expression of glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs) and the factors that affect GR function (FKBP51, Bag-1 and HSP70) in a prenatal stress animal model of depression, a model of obesity and a model of both depression and obesity...
March 9, 2018: Journal of Neuroendocrinology
Thaddeus S Block, Harvey Kushner, Ned Kalin, Craig Nelson, Joseph Belanoff, Alan Schatzberg
BACKGROUND: Patients with psychotic depression exhibit elevated cortisol levels. Competitively antagonizing cortisol at the glucocorticoid receptor with mifepristone demonstrated therapeutic benefit in early studies of patients with psychotic depression. We present a combined analysis of all controlled phase 2 and 3 studies to report antipsychotic differences between treatment with mifepristone or placebo and to evaluate the relative contributions to response of attaining an a priori-defined, high mifepristone plasma level and markers of glucocorticoid receptor antagonism (increases in adrenocorticotropin hormone and cortisol) with treatment...
January 31, 2018: Biological Psychiatry
Roseli Soncini, Joseana Vieira, Ana Carolina Ramos Lopes, Silvia Graciela Ruginsk, Erika K Incerpi, Angel Roberto Barchuk
Glucocorticoids (GCs) are used for acute respiratory distress syndrome (ARDS) to improve or prevent lung injury. The mechanisms underlying the effects of GCs involve inadequate GC-receptor (GR)-mediated downregulation of pro-inflammatory factors despite elevated levels of cortisol. Within this context, knowledge of the transcriptional pattern of the GR gene in response to variations in physiological parameters may shed light on this issue. We addressed this problem by measuring plasmatic corticosterone (CCT) levels and assessing GR expression at transcript and protein levels in rats with caecal ligation and puncture (CLP)-induced ARDS-like syndrome treated with dexamethasone and metyrapone...
March 6, 2018: Molecular and Cellular Endocrinology
Martina Blaschke, Regine Koepp, Julia Cortis, Marina Komrakova, Matthias Schieker, Ute Hempel, Heide Siggelkow
BACKGROUND: Crohn´s disease (CD) is associated with a higher prevalence of osteoporosis. The pathogenesis of bone affliction remains controversial, especially if inflammatory cytokines or glucocorticoid therapy are the main contributors. In postmenopausal osteoporosis, bone resorption is induced by IL-6, IL-1β and TNF-α. In contrast, in children with CD, IL-6 exclusively decreased bone formation without affecting bone resorption. OBJECTIVES: The objective of this study was to further clarify the pathophysiology of bone affliction in adult patients with CD with the use of an osteoblast and osteoclast cell model...
January 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
A Bárbara Garcia-Garcia, S Martinez-Hervas, J T Real, P Marin-Garcia, G de Marco, A Priego, J F Martínez-Valls, R Carmena, F J Chaves, J F Ascaso
PURPOSE: Our aim was to evaluate the postprandial effect of an oral fat load test (OFLT) rich in unsaturated fatty acids on gene expression profile in peripheral blood mononuclear cells (PBMC) from subjects with abdominal obesity as an insulin resistance model and controls. METHODS: A total of 20 controls and 20 abdominal obese patients were studied. Metabolic parameters and oxidative stress markers were measured with standardized protocols. The whole gene expression at fasting state and after the OFLT (0, 4 and 8 h) was analysed using human HT-12-v4 expression beadchips, from Illumina...
March 8, 2018: European Journal of Nutrition
N Facchinello, T Skobo, G Meneghetti, E Colletti, A Dinarello, N Tiso, R Costa, G Gioacchini, O Carnevali, F Argenton, L Colombo, L Dalla Valle
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
March 8, 2018: Scientific Reports
Wayne I Doyle, Julian P Meeks
Steroids play vital roles in animal physiology across species, and the production of specific steroids is associated with particular internal biological functions. The internal functions of steroids are, in most cases, quite clear. However, an important feature of many steroids -- their chemical stability -- allows these molecules to play secondary, external roles as chemical messengers after their excretion via urine, feces, or other shed substances. The presence of steroids in animal excretions has long been appreciated, but their capacity to serve as chemosignals has not received as much attention...
March 8, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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