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Glucocorticoid receptor ( GR )

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https://www.readbyqxmd.com/read/28223352/cross-talk-between-the-glucocorticoid-receptor-and-myod-family-inhibitor-domain-containing-protein-provides-a-new-mechanism-for-generating-tissue-specific-responses-to-glucocorticoids
#1
Robert H Oakley, John M Busillo, John A Cidlowski
Glucocorticoids are primary stress hormones that regulate many physiological processes, and synthetic derivatives of these molecules are widely used in the clinic. The molecular factors that govern tissue specificity of glucocorticoids, however, are poorly understood. The actions of glucocorticoids are mediated by the glucocorticoid receptor (GR). To discover new proteins that interact with GR and modulate its function, we performed a yeast 2-hybrid assay. The MyoD family inhibitor domain containing (MDFIC) protein was identified as a binding partner for GR...
February 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28220107/new-insights-in-glucocorticoid-receptor-signaling-more-than-just-a-ligand-binding-receptor
#2
REVIEW
Karin Scheschowitsch, Jacqueline Alves Leite, Jamil Assreuy
The clinical use of classical glucocorticoids (GC) is narrowed by the many side effects it causes and the resistance to GC observed in some diseases. Since the great majority of GC effects depend on the activation of a glucocorticoid receptor (GR), many research groups had focused to better understand the signaling pathways involving those receptors. Transgenic animal models and genetic modifications of the receptor brought a huge insight into GR mechanisms of action. This in turn opened a new window for the search of selective GR modulators that ideally may have agonistic and antagonistic combined effects and activate one specific signaling pathway, inducing mostly transrepression or transactivation mechanisms...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28212940/hippocampal-nr3c1-dna-methylation-can-mediate-part-of-preconception-paternal-stress-effects-in-rat-offspring
#3
Somayeh Niknazar, Arezo Nahavandi, Ali Asghar Peyvandi, Hassan Peyvandi, Navid Ahmady Roozbahany, Hojjat-Allah Abbaszadeh
Many studies have been shown that maternal stress during pregnancy and in early life period influences offspring in the behavioral and molecular aspects in human and animal models. Recent research has indicated that the environmental condition of males before conception has effects on next generations. We evaluated whether preconception paternal stress (PPS) could influence on hippocampal glucocorticoid receptor gene (GR), (NR3C1) expression, corticosterone response and behavioral outcomes of their offspring...
February 14, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28212463/efficacy-and-tolerability-of-an-inhaled-selective-glucocorticoid-receptor-modulator-azd5423-in-copd-patients-phase-ii-study-results
#4
Piotr Kuna, Magnus Aurivillius, Carin Jorup, Susanne Prothon, Ziad Taib, Staffan Edsbäcker
AZD5423 is a novel, inhaled, selective glucocorticoid receptor modulator (SGRM), which in an allergen challenge model in asthmatics improved lung function and airway hyper-reactivity. In the current trial, AZD5423 was for the first time tested in patients with chronic obstructive pulmonary disease (COPD). In this double-blind, randomised and parallel group study, we examined airway and systemic effects of two doses of AZD5423, inhaled via Turbuhaler for 12 weeks, in 353 symptomatic COPD patients (average pre-bronchodilator forced expiratory volume in one second (FEV1) at screening was 50-52% of predicted normal)...
February 17, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28199000/overexpression-of-pregnane-x-and-glucocorticoid-receptors-and-the-regulation-of-cytochrome-p450-in-human-epileptic-brain-endothelial-cells
#5
Chaitali Ghosh, Mohammed Hossain, Jesal Solanki, Imad M Najm, Nicola Marchi, Damir Janigro
OBJECTIVE: Recent evidence suggests a metabolic contribution of cytochrome P450 enzymes (CYPs) to the drug-resistant phenotype in human epilepsy. However, the upstream molecular regulators of CYP in the epileptic brain remain understudied. We therefore investigated the expression and function of pregnane xenobiotic (PXR) and glucocorticoid (GR) nuclear receptors in endothelial cells established from post-epilepsy surgery brain samples. METHODS: PXR/GR localization was evaluated by immunohistochemistry in specimens from subjects who underwent temporal lobe resections to relieve drug-resistant seizures...
February 15, 2017: Epilepsia
https://www.readbyqxmd.com/read/28196872/muc16-regulates-tspyl5-for-lung-cancer-cell-growth-and-chemoresistance-by-suppressing-p53
#6
Imayavaramban Lakshmanan, Shireen Salfity, Parthasarathy Seshacharyulu, Satyanarayana Rachagani, Abigail Thomas, Srustidhar Das, Prabin D Majhi, Rama Krishna Nimmakayala, Raghupathy Vengoji, Subodh M Lele, Moorthy P Ponnusamy, Surinder K Batra, Apar Kishor Ganti
PURPOSE: MUC16, a tumor biomarker and cell surface associated mucin, is overexpressed in various cancers; however, its role in lung cancer pathogenesis is unknown. Here, we have explored the mechanistic role of MUC16 in lung cancer. EXPERIMENTAL DESIGN: To identify the functional role of MUC16, stable knockdown was carried in lung cancer cells with two different shRNAs. Clinical significance of MUC16 was evaluated in lung cancer patient's tissues using IHC. We have generated genetically engineered mouse model (KrasG12D; AdCre) to evaluate the preclinical significance of MUC16...
February 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28194607/il-17a-monoclonal-antibody-partly-reverses-the-glucocorticoids-insensitivity-in-mice-exposed-to-ozonec
#7
Xia Fei, Peng-Yu Zhang, Xue Zhang, Guo-Qing Zhang, Wu-Ping Bao, Ying-Ying Zhang, Min Zhang, Xin Zhou
Exposure to ozone has been associated with airway inflammation and glucocorticoid insensitivity. This study aimed to observe the capacity of anti-murine interleukin-17A monoclonal antibody (IL-17mAb) to reverse ozone-induced glucocorticoid insensitivity and to detect its effects with glucocorticoids in protecting against airway inflammation. After C57/BL6 mice were exposed to ozone (2.5 ppm; 3 h) for 12 times over 6 weeks, PBS, IL-17mAb (50 ug/ml), dexamethasone (2 mg/kg), and combination administration of IL-17mAb (50 ug/ml) and dexamethasone (2 mg/kg) were intraperitoneally injected into mice at a dose of 0...
February 13, 2017: Inflammation
https://www.readbyqxmd.com/read/28191869/aberrant-corticosteroid-metabolism-in-tumor-cells-enables-gr-takeover-in-enzalutamide-resistant-prostate-cancer
#8
Jianneng Li, Mohammad Alyamani, Ao Zhang, Kai-Hsiung Chang, Michael Berk, Zhenfei Li, Ziqi Zhu, Marianne Petro, Cristina Magi-Galluzzi, Mary-Ellen Taplin, Jorge A Garcia, Kevin Courtney, Eric A Klein, Nima Sharifi
Prostate cancer is driven by androgen stimulation of the androgen receptor (AR). The next-generation AR antagonist, enzalutamide, prolongs survival, but resistance and lethal disease eventually prevail. Emerging data suggest that the glucocorticoid receptor (GR) is upregulated in this context, stimulating expression of AR-target genes that permit continued growth despite AR blockade. However, countering this mechanism by administration of GR antagonists is problematic because GR is essential for life. We show that enzalutamide treatment in human models of prostate cancer and patient tissues is accompanied by a ubiquitin E3-ligase, AMFR, mediating loss of 11β-hydroxysteroid dehydrogenase-2 (11β-HSD2), which otherwise inactivates cortisol, sustaining tumor cortisol concentrations to stimulate GR and enzalutamide resistance...
February 13, 2017: ELife
https://www.readbyqxmd.com/read/28185867/an-experimental-evaluation-of-the-role-of-the-stress-axis-in-mediating-predator-prey-interactions-in-wild-marine-fish
#9
Michael J Lawrence, Erika J Eliason, Jacob W Brownscombe, Kathleen M Gilmour, John W Mandelman, Steven J Cooke
The hypothalamic-pituitary-interrenal (HPI) axis, through corticosteroid secretion, is an integral mechanism regulating internal homeostasis when vertebrates are faced with a stressor. However, continued HPI-axis stimulation can produce homeostatic overload, where corticosteroids are detrimental to organismal function. This overload condition may play an important role in mediating predator-prey interactions, because chronically/previously stressed animals may have higher rates of predator-induced mortality...
February 7, 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/28174120/xenobiotics-and-the-glucocorticoid-receptor
#10
REVIEW
Linda S M Gulliver
Glucocorticoid Receptor (GR) is present in virtually every human cell type. Representing a nuclear receptor superfamily, GR has several different isoforms essentially acting as ligand-dependent transcription factors, regulating glucocorticoid-responsive gene expression in both a positive and a negative manner. Although the natural ligand of the Glucocorticoid Receptor, glucocorticoids (GC) represent only some of the multiple ligands for GR. Xenobiotics, ubiquitous in the environment, bind to GR and are also capable of activating or repressing GR gene expression, thereby modulating GR cell and tissue-specific downstream effects in a multitude of ways that include responses to inflammatory, allergic, metabolic, neoplastic and autoimmune processes...
February 4, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28166946/preventive-effects-of-supplemental-dietary-zinc-on-heat-induced-damage-in-the-epididymis-of-boars
#11
Zhaojian Li, Yansen Li, Xin Zhou, Yun Cao, Chunmei Li
Hyperthermia in boars reduces growth performance and sperm production. Zinc is an essential trace element in animal nutrition. Here we investigate the effects of dietary zinc on epididymal structure and function in Bama miniature pigs treated with heat exposure and investigate approaches to improve the reproductive performance in summer. Male Bama miniature pigs (n=18; aged 6 months; bodyweight=10.79±0.06kg) were randomly allocated to 3 groups: control group (Control), heat treatment group (HT), and the diet-supplemented and heat treatment group (H+Zn)...
February 2017: Journal of Thermal Biology
https://www.readbyqxmd.com/read/28139699/genome-wide-regulatory-roles-of-the-c2h2-type-zinc-finger-protein-znf764-on-the-glucocorticoid-receptor
#12
Abeer Fadda, Najeeb Syed, Rafah Mackeh, Anna Papadopoulou, Shigeru Suzuki, Puthen V Jithesh, Tomoshige Kino
The C2H2-type zinc finger protein ZNF764 acts as an enhancer for several steroid hormone receptors, and haploinsufficiency of this gene may be responsible for tissue resistance to multiple steroid hormones including glucocorticoids observed in a patient with 16p11.2 microdeletion. We examined genome-wide regulatory actions of ZNF764 on the glucocorticoid receptor (GR) in HeLa cells as a model system. ZNF764- and GR-binding sites demonstrated similar distribution in various genomic features. They positioned predominantly around 50-500 kbs from the transcription start sites of their nearby genes, and were closely localized with each other, overlapping in ~37% of them...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28137450/crf1-receptor-deficiency-increases-cocaine-reward
#13
Angelo Contarino, Pierre Kitchener, Monique Vallée, Francesco Papaleo, Pier-Vincenzo Piazza
Stimulant drugs produce reward but also activate stress-responsive systems. The corticotropin-releasing factor (CRF) and the related hypothalamus-pituitary-adrenal (HPA) axis stress-responsive systems are activated by stimulant drugs. However, their role in stimulant drug-induced reward remains poorly understood. Herein, we report that CRF1 receptor-deficient (CRF1-/-), but not wild-type, mice show conditioned place preference (CPP) responses to a relatively low cocaine dose (5 mg/kg, i.p.). Conversely, wild-type, but not CRF1-/-, mice display CPP responses to a relatively high cocaine dose (20 mg/kg, i...
January 27, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28135675/blunted-hpa-axis-activity-prior-to-suicide-attempt-and-increased-inflammation-in-attempters
#14
Nadine M Melhem, Sara Munroe, Anna Marsland, Katarina Gray, David Brent, Giovanna Porta, Antoine Douaihy, Mark L Laudenslager, Frank DePietro, Rasim Diler, Henry Driscoll, Priya Gopalan
BACKGROUND: Hypothalamic-Pituitary-Adrenal (HPA) axis dysregulation is associated with increased risk for suicidal behavior. However, it is not clear whether such dysregulation exists prior to or is a consequence of attempt. Studies also show an activation of inflammatory responses in suicidal behavior but often combine attempters with those with ideation. METHODS: The sample consisted of psychiatric inpatients, aged 15-30 years, admitted for suicide attempt (SA, n=38), inpatients admitted for suicidal ideation with no prior history of attempts (SI, n=40), and healthy controls (n=37)...
January 10, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28115641/endocrine-activity-of-avb-2mr-bha-and-their-mixtures
#15
Ivana Klopčič, Marija Sollner Dolenc
Personal care products are used increasingly, resulting in growing concern concerning their potential disruption of normal hormonal functions. Recent results on the bioaccumulation of cosmetic ingredients in wildlife and humans point to the need for an in-depth analysis for endocrine activity, in particular with respect to their influence on the androgen (AR), glucocorticoid (GR) and thyroid hormone receptors (TR). Furthermore, humans are commonly exposed simultaneously to complex mixtures of endocrine active compounds...
January 22, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28102225/glucocorticoid-receptor-signalling-activates-yap-in-breast-cancer
#16
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
#17
Cherish Chong, Anis Hamid, Tham Yao, Amanda E Garza, Luminita H 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)...
March 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
#18
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
#19
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 14, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28089704/brain-mineralocorticoid-receptor-function-in-control-of-salt-balance-and-stress-adaptation
#20
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
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