• GCs activated consensus hypoxia response element (HRE) reporters in a glucocorticoid receptor (GR)-dependent manner. (ox.ac.uk)
  • Compounds 1-5 showed -12.53 to -10.11 kcal/mol potential binding affinity with glucocorticoid receptor (GR) and good ADME profile. (hindawi.com)
  • They mediate their signals by specific receptor protein, namely, glucocorticoid receptor (GR). The GR is a transcription factor classified within the nuclear receptor (NR) superfamily and consists of three conserved domains: an N-terminal transactivation domain, a central DNA-binding domain (DBD), and a C-terminal ligand-binding domain (LBD) [ 2 ]. (hindawi.com)
  • In the process they explored the intersection of lysosomal degradation pathways and glucocorticoid receptor signaling. (promegaconnections.com)
  • Although many affected biological pathways are typically regulated by the glucocorticoid receptor (GR), during sepsis this is deficient and supplementation with exogenous glucocorticoids is often ineffective in reducing mortality. (suny.edu)
  • The diverse effects of glucocorticoids are mediated by the glucocorticoid receptor (GR). Unliganded GR is retained in the cytosol by heat shock proteins that are released upon binding and activation by glucocorticoid [ 3 ]. (biomedcentral.com)
  • Furthermore, we have investigated the role of pre-receptor modulation of glucocorticoid availability by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in these processes. (birmingham.ac.uk)
  • We developed a structured model of the HPA axis that includes the glucocorticoid receptor (GR). This model incorporates nonlinear kinetics of pituitary GR synthesis. (biomedcentral.com)
  • Glucocorticoid receptor-induced MAPK phosphatase-1 (MPK-1) expression inhibits paclitaxel-associated MAPK activation and contributes to breast cancer cell survival. (uchicago.edu)
  • Glucocorticoid receptor activation signals through forkhead transcription factor 3a in breast cancer cells. (uchicago.edu)
  • Activation of the glucocorticoid receptor is associated with poor prognosis in estrogen receptor-negative breast cancer. (uchicago.edu)
  • Glucocorticoid receptor activity contributes to resistance to androgen-targeted therapy in prostate cancer. (uchicago.edu)
  • Glucocorticoid receptor antagonism as a novel therapy for triple-negative breast cancer. (uchicago.edu)
  • Glucocorticoid receptor activation inhibits chemotherapy-induced cell death in high-grade serous ovarian carcinoma. (uchicago.edu)
  • Hsp90 Inhibition Results in Glucocorticoid Receptor Degradation in Association with Increased Sensitivity to Paclitaxel in Triple-Negative Breast Cancer. (uchicago.edu)
  • Selective Glucocorticoid Receptor Modulators (SGRMs) Delay Castrate-Resistant Prostate Cancer Growth. (uchicago.edu)
  • Discovery of a Glucocorticoid Receptor (GR) Activity Signature Using Selective GR Antagonism in ER-Negative Breast Cancer. (uchicago.edu)
  • Glucocorticoid receptor modulation decreases ER-positive breast cancer cell proliferation and suppresses wild-type and mutant ER chromatin association. (uchicago.edu)
  • Insulin potentiates the transactivation potency of the glucocorticoid receptor. (shengsci.com)
  • This requires the presence of active glucocorticoid receptor (GR) since the response is significantly inhibited by the anti-glucocorticoid RU30406. (shengsci.com)
  • Notably, emerging evidence indicates that the glucocorticoid receptor (GR) has drawn considerable interest in ovarian cancer development. (biomedcentral.com)
  • Glucocorticoid action in cells is mediated by the glucocorticoid receptor (GR), a member of the superfamily of ligand-inducible transcription factors that exert a variety of physiological functions, such as inflammation, autoimmune diseases, and cancer [ 4 ]. (biomedcentral.com)
  • The glucocorticoid receptor also known as NR3C1 is the receptor to which cortisol and other glucocorticoids bind. (absoluteastronomy.com)
  • Dexamethasone binds more powerfully to the glucocorticoid receptor than cortisol does. (wikidoc.org)
  • Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger similar effects. (wikidoc.org)
  • Glucocorticoids bind to the cytosolic glucocorticoid receptor . (wikidoc.org)
  • After a hormone binds to the corresponding receptor, the newly-formed receptor-ligand complex translocates itself into the cell nucleus , where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes . (wikidoc.org)
  • To the end right here we display that coupling a hydrophobic label for an androgen receptor agonist changes it to a powerful Selective Androgen Receptor Degrader (SARD) with the capacity of inducing >50% of AR degradation (DC50) at 1 μM. (buyresearchchemicalss.net)
  • Hypothesizing that improved AR amounts may drive the introduction of CRPC and taking into consideration Ibuprofen Lysine (NeoProfen) the medical success from the selective estrogen receptor degrader (SERD) fulvestrant[23] we wanted to induce AR degradation via our hydrophobic tagging strategy. (buyresearchchemicalss.net)
  • the glucocorticoid receptor (GR) another steroid receptor not really identified by the mother or father ligand RU59063 isn't degraded in LNCaP cells under circumstances that bring about near-complete degradation from the androgen receptor. (buyresearchchemicalss.net)
  • Familial glucocorticoid receptor haploinsufficiency by non-sense mediated mRNA decay, adrenal hyperplasia and apparent mineralocorticoid excess. (hal.science)
  • Primary glucocorticoid resistance (OMIM 138040) is a rare hereditary disease that causes a generalized partial insensitivity to glucocorticoid action, due to genetic alterations of the glucocorticoid receptor (GR). Investigation of adrenal incidentalomas led to the discovery of a family (eight affected individuals spanning three generations), prone to cortisol resistance, bilateral adrenal hyperplasia, arterial hypertension and hypokalemia. (hal.science)
  • Methods: We have characterised the impact of glucocorticoids upon key metabolic pathways and processes regulating muscle size and mass including: protein synthesis, protein degradation and myoblast proliferation in both murine C2C12 and human primary myotube cultures. (birmingham.ac.uk)
  • Results: Corticosterone decreased myotube area, decreased protein synthesis and increased protein degradation in murine myotubes. (birmingham.ac.uk)
  • These findings were endorsed in human primary myotubes where cortisol also decreased protein synthesis and increased protein degradation. (birmingham.ac.uk)
  • Selective 11β-HSD1 inhibition blocked the decrease in protein synthesis, increased in protein degradation and reduction in myotube area induced by 11-dehydrocorticosterone/cortisone. (birmingham.ac.uk)
  • As discovered in 2010, cereblon plays a crucial role in protein degradation but also was the culprit in thalidomide-associated teratogenicity. (medpagetoday.com)
  • Acute stress increases glutamate release, membrane trafficking of AMPA and NMDA receptors, and potentially glutamate clearance in the prefrontal cortex through various mechanisms that involve glucocorticoid regulation. (nature.com)
  • Recent studies have shed light on the mechanisms by which stress and glucocorticoids affect glutamate transmission, including effects on glutamate release, glutamate receptors and glutamate clearance and metabolism. (nature.com)
  • Exhibits no significant effect on glucocorticoid, estrogen or progesterone receptors at concentrations inducing AR degradation. (tocris.com)
  • Present investigation deals to find potential agonist of glucocorticoid receptors after biotransformation of betamethasone dipropionate (1) and to carry out the molecular docking and ADME analyses. (hindawi.com)
  • Steroid hormones can be grouped into five groups by the receptors to which they bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestogens. (absoluteastronomy.com)
  • Glucocorticoids are distinguished from mineralocorticoids and sex steroids by the specific receptors, target cells, and effects. (wikidoc.org)
  • Glucocorticoid receptors are found in the cells of almost all vertebrate tissues. (wikidoc.org)
  • Glucocorticoid (GC) and hypoxic transcriptional responses play a central role in tissue homeostasis and regulate the cellular response to stress and inflammation, highlighting the potential for cross-talk between these two signaling pathways. (ox.ac.uk)
  • The chemical reactions and pathways resulting in the breakdown of glucocorticoids, hormonal C21 corticosteroids synthesized from cholesterol. (planteome.org)
  • The expression levels of muscle degradation-related signaling pathways, such as the Klf15, Redd-1, FoxO3a, Atrogin-1, and MuRF1 pathways, were enhanced by CUMS and attenuated by RG. (bvsalud.org)
  • With the hypothesis that liver-specific glucocorticoid therapy will be more clinically beneficial than systemic therapy, we studied liver-specific GR effects in infection, inflammation, or sepsis. (suny.edu)
  • We hypothesized that endothelial glycocalyx degradation is associated with the volume of intravenous fluids administered during early sepsis resuscitation. (biomedcentral.com)
  • We used mass spectrometry to measure plasma heparan sulfate (a highly sensitive and specific index of systemic endothelial glycocalyx degradation) after 6 h of intravenous fluids in 56 septic shock patients, at presentation and after 24 h of intravenous fluids in 100 sepsis patients, and in two groups of non-infected patients. (biomedcentral.com)
  • Glycocalyx degradation occurs in sepsis and septic shock and is associated with in-hospital mortality. (biomedcentral.com)
  • The most common class of steroids is glucocorticoids that comprise betamethasone, methylprednisolone, dexamethasone, and prednisolone. (hindawi.com)
  • In a recent article published in Science Signaling , Yuangheng He and colleagues asked how the weak alkaline compound chloroquine (CQ) enhances the anti-inflammatory effects of synthetic glucocorticoids like dexamethasone, which are used to treat a host of inflammatory and autoimmune diseases. (promegaconnections.com)
  • Dexamethasone (Dex) is a potent synthetic member of the glucocorticoid (GC) class of steroid drugs that are widely used to regulate various developmental and metabolic processes including bone remodeling.1 However side effects including bone loss low bone mineral density and increased fracture risk limit long-term use of GCs. (technuc.com)
  • Stress seems to affect the integrity of skin collagen through glucocorticoid-mediated processes that alter its synthesis and degradation. (nih.gov)
  • While glucocorticoids initiate endocannabinoid synthesis in neurons, this study was undertaken to test whether cortisol also regulates endocannabinoid levels in mesenchymal cells such as SFs, and whether this interferes with integrin-mediated adhesion. (uni-regensburg.de)
  • Glucocorticoids (GCs) promote muscle degradation and inhibit muscle synthesis, eventually causing muscle atrophy. (bvsalud.org)
  • Autophagy can be seen as a the sequestration of mass cytoplasm and organelles in dual- or multi-membrane autophagic vesicles and their following degradation by lysosomes for macromolecular synthesis and ATP era.13 Several research have proven that autophagy regulates cell proliferation and function Cisplatin of osteoclasts 14 osteoblasts 15 and osteocytes 16 recommending that autophagy can be an important process for bone tissue homeostasis. (technuc.com)
  • Glucocorticoids (GCs), a group of steroid hormones, regulate various metabolic and homeostatic functions including growth, apoptosis, developmental behavior, and inflammation that are necessary for life [ 1 ]. (hindawi.com)
  • Background: The adverse metabolic effects of prescribed and endogenous glucocorticoid excess, 'Cushing's syndrome', create a significant health burden. (birmingham.ac.uk)
  • Enhancing the expression of enzymes involved in gluconeogenesis is probably the best-known metabolic function of glucocorticoids. (wikidoc.org)
  • The ordinary glucocorticoids do not distinguish among transactivation and transrepression and influence both the "wanted" immune and "unwanted" genes regulating the metabolic and cardiovascular functions. (wikidoc.org)
  • The robust anti-inflammatory effects of glucocorticoids are applied broadly in the clinical setting to treat diverse conditions, including rheumatic diseases, allergy, skin disorders, pulmonary conditions, cancer, transplant rejection, and even spinal cord injury. (biomedcentral.com)
  • The stability against degradation during inflammation, as can occur in osteoarthritis, is also part of the investigation. (donau-uni.ac.at)
  • Conclusion: Glucocorticoids are potent regulators of skeletal muscle protein homeostasis and myoblast proliferation. (birmingham.ac.uk)
  • Glucocorticoids have potent anti-inflammatory and immunosuppressive properties. (wikidoc.org)
  • A variety of synthetic glucocorticoids, some far more potent than cortisol, have been created for therapeutic use. (wikidoc.org)
  • As a consequence, glucocorticoids are widely used as drugs to treat inflammatory conditions such as arthritis and dermatitis , and as adjunction therapy for conditions such as autoimmune diseases . (wikidoc.org)
  • The use of both betamethasone and budesonide poses an environmental risk, and exchange with synthetic glucocorticoids with a lower environmental risk is to be advocated in cases where it is possible from a clinical perspective. (janusinfo.se)
  • Note that corresponding environmental risk assessments have not been made for other synthetic glucocorticoids that are available on the Swedish market, and which could possibly constitute exchange alternatives. (janusinfo.se)
  • These outcomes claim that selective AR degradation could be an effective restorative prostate Ibuprofen Lysine (NeoProfen) tumor technique in the framework of AR mutations that confer level of resistance to third era AR antagonists. (buyresearchchemicalss.net)
  • Glucocorticoids also affect skin quality through modulation of the immune system. (nih.gov)
  • Once activated the GR translocates to the nucleus and can bind directly to glucocorticoid response elements (GREs) as a homodimer, resulting in both activation and repression of transcription, depending on promoter structure and interaction with various co-activators and co-repressors. (biomedcentral.com)
  • This active form of vitamin D can inhibit immune cell proliferation, promote an anti-inflammatory cytokine profile, expand regulatory T cells, enhance glucocorticoid actions, increase glutathione production, and inhibit hepatic stellate cells. (springer.com)
  • Vitamin D deficiency has been commonly present in patients with immune-mediated liver and non-liver diseases, and it has been associated with histological severity, advanced hepatic fibrosis, and non-response to conventional glucocorticoid therapy in autoimmune hepatitis. (springer.com)
  • This study aimed to determine the therapeutic window and achieve rapid, prolonged, and maximal substrate degradation for rapid disease response while mitigating hematologic toxic effects," the authors wrote in conclusion. (medpagetoday.com)
  • Mounting evidence suggests that stress, along with the associated hormonal and neurochemical mediators (particularly glucocorticoids), induces changes in glutamate release, transmission and metabolism in cortical and limbic brain areas, thereby influencing cognitive and emotional processing and behaviour. (nature.com)
  • Mounting evidence suggests that acute and chronic stress, especially the stress-induced release of glucocorticoids, induces changes in glutamate neurotransmission in the prefrontal cortex and the hippocampus, thereby influencing some aspects of cognitive processing. (nature.com)
  • Unfortunately, the long-term clinical utility of glucocorticoids is limited by undesirable adverse effects, including suppression of the hypothalamus-pituitary-adrenal (HPA) axis, increased serum glucose, induction of osteoporosis and glaucoma, altered electrolyte balance, insomnia, and other behavioral alterations. (biomedcentral.com)
  • The HPA axis is activated in response to real or perceived stressors and culminates in the production and secretion of glucocorticoids by the adrenal glands. (nature.com)
  • Betamethasone is an important glucocorticoids (GCs), frequently used to cure allergies (such as asthma and angioedema), Crohn's disease, skin diseases (such as dermatitis and psoriasis), systemic lupus erythematosus, rheumatic disorders, and leukemia. (hindawi.com)
  • An increasing stability was identified in the order from non-halogenated steroids (e.g. hydrocortisone), over 9α-halogenated steroids (e.g. betamethasone), to C17-monoesters (e.g. betamethasone 17-valerate, clobetasol propionate), and finally to acetonides (e.g. triamcinolone acetonide), thus suggesting a strong relationship of the biodegradability with the glucocorticoid structure. (hbz-nrw.de)
  • Persistence: '78% degradation of betamethasone was observed in the OECD 302B/314B study within 14 days but it does not pass the criteria of inherent biodegradability. (janusinfo.se)
  • The compounds were accurately selected to cover manifold structural moieties of commonly used glucocorticoids, including non-halogenated and halogenated steroids, their mono- and diesters, and several acetonide-type steroids. (hbz-nrw.de)
  • An alternative to this medicinal chemistry approach is a systems biology based strategy that seeks to amplify selectively the anti-inflammatory activity of very low dose glucocorticoid in immune cells without modulating alternative cellular networks that mediate glucocorticoid toxicity. (biomedcentral.com)
  • For instance SARD279 where the adamantyl moiety can be combined to RU59063 with a 8 atom ester linkage decreased AR proteins amounts by 50% at 1 μM (DC50) (Shape 1B) while no degradation was recognized in cells treated using the parental AR ligand. (buyresearchchemicalss.net)
  • At the current time, intensive research is aimed at discovering selectively acting glucocorticoids that will be able to repress only the immune system. (wikidoc.org)
  • A single copy of a glucocorticoid-responsive element (GRE) is sufficient in mediating the combinatorial response of a promoter to both glucocorticoids and insulin in HepG2 cells. (shengsci.com)
  • In vitro studies showed the mezigdomide-induced degradation of the two factors enhanced cytotoxic effects in myeloma cells, including cells resistant to IMiDs lenalidomide (Revlimid) and pomalidomide (Pomalyst) and with cereblon down-regulation. (medpagetoday.com)
  • Previous efforts to design glucocorticoid structures with an increased therapeutic window have focused on dissociating anti-inflammatory transcriptional repression from adverse effects primarily driven by transcriptional activation. (biomedcentral.com)
  • These data suggest that the multi-target mechanism of low-dose prednisolone and dipyridamole creates a dissociated activity profile with an increased therapeutic window through cellular network selective amplification of glucocorticoid-mediated anti-inflammatory signaling. (biomedcentral.com)
  • Development of glucocorticoids with an improved therapeutic window has therefore been an area of focus for multiple groups. (biomedcentral.com)
  • Since AEA levels are regulated by COX-2 and FAAH, inhibition of both enzymes along with low-dose glucocorticoids may provide a therapeutic option to maximally boost the endocannabinoid system in RA, with possible beneficial effects. (uni-regensburg.de)
  • The immunomodulatory effects of glucocorticoids (GCs) have been described as bimodal, with high levels of GCs exerting immunosuppressive effects and low doses of GCs being immunopermissive. (aai.org)
  • Glucocorticoids are a mainstay of anti-inflammatory therapy, but significant adverse effects ultimately limit their utility. (biomedcentral.com)
  • The combination of prednisolone and the antithrombotic drug dipyridamole was profiled using in vitro and in vivo models of anti-inflammatory activity and glucocorticoid-induced adverse effects to demonstrate a dissociated activity profile. (biomedcentral.com)
  • The immune-specific amplification of prednisolone anti-inflammatory activity by dipyridamole did not extend to glucocorticoid-mediated adverse effects, including corticosterone suppression or increased expression of tyrosine aminotransferase, in vivo after repeat dosing in rats. (biomedcentral.com)
  • Our data underscores the potential use of selective 11β-HSD1 inhibitors to ameliorate muscle-wasting effects associated with glucocorticoid excess. (birmingham.ac.uk)
  • Glucocorticoids have multiple effects on fetal development. (wikidoc.org)
  • Excessive glucocorticoid levels resulting from administration as a drug or hyperadrenocorticism have effects on many systems. (wikidoc.org)
  • Relative to their binding affinities the synthesized SARDs induced AR degradation at sub-micromolar concentrations. (buyresearchchemicalss.net)
  • The name glucocorticoid derives from early observations that these hormones were involved in glucose metabolism . (wikidoc.org)
  • Identification of the mechanisms important for the stability and/or degradation of Myconcoproteins, the most commonly de-regulated oncoprotein in human cancers. (sciforschenonline.org)
  • Our findings indicate that glucocorticoid-induced adhesion is dependent on CB(1) /CB(2) /TRPV-1 activation. (uni-regensburg.de)
  • Long-term use of glucocorticoids is a widespread clinical problem which currently has no effective solution other than discontinuing the use. (technuc.com)
  • These include direct myotoxicity (caused by alcohol, cocaine, glucocorticoids, and statins, amongst others), immunologically-induced inflammatory myopathy (caused by D-penicillamine, statins, and anti-cancer drugs), and indirect SKM injury (occurs as a result of a variety of different mechanisms). (degruyter.com)
  • Brings about degradation of ARs in VCaP and LNCaP prostate cancer cell lines (D max = 98% at 12h) in a proteasome-dependent manner, and inhibits cell proliferation. (tocris.com)
  • Glucocorticoids are able to prevent the transcription of any of immune genes, including the IL-2 gene. (wikidoc.org)
  • The work also is fascinating because it takes a systems-view of a biological question: How is it that the drug chloroquine just happens to influence glucocorticoid signaling? (promegaconnections.com)
  • Persistence: 'Inherent degradability: 28% primary degradation in 28 days (OECD 302C) (Reference 5). (janusinfo.se)
  • The Nobel Prize in Medicine was awarded to Kendall, Reichstein, and Hench in 1950 for their seminal work in elucidating the chemical structure of glucocorticoids (GCs) 3 and their use as effective therapy to reduce the pathological consequences of rheumatoid arthritis (www.noble.org). (aai.org)