Дисертації з теми "Récepteurs glucocorticoïdes"
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Sablonnière, Bernard. "Organisation hétéro-oligomérique du récepteur des glucocorticoi͏̈des." Lille 1, 1988. http://www.theses.fr/1988LIL10117.
Ambroggi, Frédéric. "Identification de la cible cellulaire des effets des glucocorticoïdes." Bordeaux 2, 2005. http://www.theses.fr/2005BOR21303.
Lustenberger, Patrick. "La chromatographie d'affinité des récepteurs des hormones stéroïdes : application à la purification du récepteur des glucocorticoi͏̈des du foie de lapin." Lille 1, 1986. http://www.theses.fr/1986LIL10137.
Belahsen, Youness. "Purification et caractérisation du récepteur des glucocorticoïdes sous forme transformée." Lille 1, 1987. http://www.theses.fr/1987LIL10045.
Carillo, Conesa María-Ángeles. "Le rôle des glucorticoïdes et du récepteur des glucorticoïdes dans les processus de neurodegenerescence et d'inflammation dans le Système Nerveux Central." Paris 6, 2011. http://www.theses.fr/2011PA066688.
Kootar, Scherazad. "L’importance des récepteurs aux glucocorticoïdes dans la physiopathologie de la maladie d’Alzheimer." Thesis, Université Côte d'Azur (ComUE), 2017. http://www.theses.fr/2017AZUR4015/document.
Strong evidence shows that oligomeric forms of the amyloid-ß peptide (oAß) cause synapse dysfunction promoting loss of hippocampus-dependent memories in the early phase of Alzheimer’s disease (AD). AD is also associated with Hypothalamus-Pituitary-Adrenal (HPA) axis dysfunction which results in an increase of glucocorticoids (CORT) activating glucocorticoid receptors (GRs). We showed that subchronic GR antagonist in 4 month Tg2576 (Tg+) mice could rescue the synaptic deficit and memory impairment (Lanté et al., 2015).In this context, we studied the contribution of GRs to AD physiopathology. Dysregulated HPA axis was characterized by increased CORT levels at 4 and 6 months of age and by loss of CORT feedback inhibition in the Tg+ mice. We further crossed the Tg+ with GRlox/lox to produce GRlox/loxTg+ mice. These mice innately exhibited high CORT levels from weaning period and due to other several unforeseen reasons, we discontinued using this new mouse model. Instead, to identify the functional relationship between the GRs and oAß at synapses, we shifted to acute oAß treatment in neurons in vitro and ex-vivo hippocampus slices. In neuron cultures, GR levels increased in the post synaptic density upon acute oAß treatment. Further, treatment of oAß on ex-vivo hippocampus slices after either pharmacological blocking of GR or genetic ablation, prevented the oAβ-dependent LTP impairment. To conclude, our results with the Tg+ mice suggest that a neuroendocrine dysregulation occurs during the onset of AD pathology. Additionally, we have evidence for a functional relationship between oAß and GRs with GRs at the synapse playing an important role in acute Aß-induced synapto-toxicity
Kootar, Scherazad. "L’importance des récepteurs aux glucocorticoïdes dans la physiopathologie de la maladie d’Alzheimer." Electronic Thesis or Diss., Université Côte d'Azur (ComUE), 2017. http://www.theses.fr/2017AZUR4015.
Strong evidence shows that oligomeric forms of the amyloid-ß peptide (oAß) cause synapse dysfunction promoting loss of hippocampus-dependent memories in the early phase of Alzheimer’s disease (AD). AD is also associated with Hypothalamus-Pituitary-Adrenal (HPA) axis dysfunction which results in an increase of glucocorticoids (CORT) activating glucocorticoid receptors (GRs). We showed that subchronic GR antagonist in 4 month Tg2576 (Tg+) mice could rescue the synaptic deficit and memory impairment (Lanté et al., 2015).In this context, we studied the contribution of GRs to AD physiopathology. Dysregulated HPA axis was characterized by increased CORT levels at 4 and 6 months of age and by loss of CORT feedback inhibition in the Tg+ mice. We further crossed the Tg+ with GRlox/lox to produce GRlox/loxTg+ mice. These mice innately exhibited high CORT levels from weaning period and due to other several unforeseen reasons, we discontinued using this new mouse model. Instead, to identify the functional relationship between the GRs and oAß at synapses, we shifted to acute oAß treatment in neurons in vitro and ex-vivo hippocampus slices. In neuron cultures, GR levels increased in the post synaptic density upon acute oAß treatment. Further, treatment of oAß on ex-vivo hippocampus slices after either pharmacological blocking of GR or genetic ablation, prevented the oAβ-dependent LTP impairment. To conclude, our results with the Tg+ mice suggest that a neuroendocrine dysregulation occurs during the onset of AD pathology. Additionally, we have evidence for a functional relationship between oAß and GRs with GRs at the synapse playing an important role in acute Aß-induced synapto-toxicity
Burollaud, Thierry. "Etude du site actif du récepteur des glucocorticoi͏̈des : modalités comparées de son interaction avec les stéroi͏̈des agonistes et antagonistes." Lille 1, 1993. http://www.theses.fr/1993LIL10091.
Formstecher, Pierre. "Le site de liaison aux stéroi͏̈des du récepteur des glucocorticoïdes : caractérisation à l'aide de sondes moléculaires diverses." Lille 1, 1986. http://www.theses.fr/1986LIL10136.
Muller, Caroline. "Etude du mécanisme d'action anti-glucocorticoïde des dérivés 7-hydroxylés de la déhydroépiandrostérone." Paris, CNAM, 2006. http://www.theses.fr/2006CNAM0554.
Experiments with a confocal microscope with a COS cell line transfected with the human glucocorticoid receptor (hGR) showed that dehydroepiandrosterone (DHEA) and its 7-hydroxylated derivatives do not modify the location of the receptor and do not prevent the nuclear transfer of hGR. These steroids had no effect on the transactivation activity of hGR. Thus, these neurosteroids were inactive on this model and their genomic action through the GR could be excluded. The human 11β-hydroxysteroid dehydrogenase type 1 (h11β-HSD1) was expressed in the yeast and each of the enzyme-catalyzed reactions were analyzed. The inter-conversion of the 7-hydroxylated DHEA metabolites was demonstrated as well as the oxidoreduction of cortisol and cortisone. A competition for the binding with the h11β-HSD1 may take place between these steroids and the glucocorticoid activation process, the former triggering immunity and the latter suppressing it
Boucher, Éric. "Développement pulmonaire murin : étude du métabolisme des androgènes, des progestines et des glucocorticoïdes." Doctoral thesis, Université Laval, 2013. http://hdl.handle.net/20.500.11794/25239.
Steroid hormones such as progestogens, estrogens, androgens and glucocorticoids are known modulators of lung development. Several elements concerning the role and regulation of steroid action in the developing lung, especially for the saccular and alveolar stages, remain to be investigated. First, a qPCR analysis of 17β-hydroxysteroid dehydrogenases (17β-HSD) type 1, 2 and 5, of 5α-réductase type 1, of m3α-HSD and of androgen receptor (AR) was performed during the saccular and alveolar stages of mouse lung development. AR expression showed a statistically significant increase during the alveolar stage while levels of 17β-HSD 2 expression decreased at the end of the saccular stage and remained low throughout the alveolar period. The androgen receptor (AR) protein was primarily detected in the nucleus of airway epithelial cells and of a subset of respiratory epithelial cells. 17β-HSD 2 mRNA was co-localized with AR protein during the saccular stage, but was absent from airway epithelium during the alveolar stage. Second, androgen and estrogen levels were measured in the murine developing lung from the canalicular to the alveolar stage. Significant difference of androgen levels between lung and control tissue. This fact added to the nuclear localization of AR is compatible with the presence of a regulated androgen metabolism during lung development. Third, expression of 20α-HSD and of the genes associated with the adrenal glucocorticoid synthesis pathway was characterized in the developing lung, from GD 15.5 to PN 15. Finally, corticosterone synthesis was only observed in a fraction of lung explants from gestation day (GD) 15.5. This observation and strong expression of 21-hydroxylase, of 20α-HSD and of 5α-reductase activities suggests local regulation of GC action. It thus appears that the actions of androgens and of glucocorticoids are both regulated at a pre-receptor level in the developing lung from the canalicular stage until the end of the alveolar stage.
Audet-Walsh, Étienne. "Régulation des gènes CYP2B de rongeurs par le récepteur des glucocorticoïdes." Thesis, Université Laval, 2008. http://www.theses.ulaval.ca/2008/25784/25784.pdf.
Vitellius, Géraldine. "Implication du récepteur des glucocorticoïdes en physiopathologie humaine." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS256.
Glucocorticoids (GC) regulate many essential biological functions by activating the glucocorticoid receptor (GR). GR loss-of function mutations are responsible for GC resistance syndrome, often associated with high blood pressure, hirsutism, bilateral adrenal hyperplasia (BAH) and obesity. Herein, functional characterization of 13 GR variants is presented (expression and binding studies, transactivation assays, subcellular localization) 6 variants were discovered with next-generating sequencing and had no functional impact on GR signaling while 7 GR loss-of-function mutations were mainly discovered during the National Clinical Hospital Research Program, Muta-GR. This PHRC discloses a 5% prevalence of GR loss-of-function mutations in a cohort of 100 patients with BAH, biological hypercortisolism and/or hypertension without Cushing signs. A GR haploinsuffisiency was demonstrated by a reduced dexamethasone-induced FKBP5 expression in skin fibroblasts of some patients harbouring GR loss-of-function mutations. These patients often presented with hypercorticism, hypokalemia, low renin and aldosterone levels, consistent with a pseudohypermineralocorticism. We showed that HSD11B2 encoding the 11β-HSD2 enzyme inactivating GC, is a direct GR target gene by transient transfection of reporter gene, RT-qPCR, LC/MSMS and ChIP. We failed to introduce GR loss-of-function mutations in human preadipocytes and adrenocortical cells by Crispr/Cas 9 technology. This work should facilitate selection of patients in whom GR mutation may be search, enabling an appropriate follow-up
Idziorek, Thierry. "Caractérisation du récepteur à hormones glucocorticoïdes du foie de rat purifié sous forme non activée." Lille 1, 1985. http://www.theses.fr/1985LIL10079.
Sarrazin, Nadège. "Recherche des cibles cellulaires et moléculaires des glucocorticoïdes à la base des pathologies reliées au stress : étude par une appproche de transgénèse conditionnelle chez la souris." Bordeaux 2, 2008. http://www.theses.fr/2008BOR21586.
Villeneuve, Annie. "Rôle de l'endothéline-1 et de ses récepteurs dans l'hypertension induite par les glucocorticoïdes." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0019/MQ56980.pdf.
Canet, Geoffrey. "Rôle central des glucocorticoïdes et de leurs récepteurs dans l’étiologie de la Maladie d’Alzheimer." Thesis, Montpellier, 2020. http://www.theses.fr/2020MONTT019.
Alzheimer's disease (AD) is characterized in the brain by the aggregation of β-amyloid peptides (Aβ) from the cleavage of the amyloid precursor protein (APP), and by the hyperphosphorylation of the Tau protein. In AD, cognitive deficits are associated with an early dysregulation of the endocrine stress axis (hypothalamic-pituitary-adrenal axis or HPA), the consequent overproduction of glucocorticoids (GC) and the alteration of their receptors (GR). Numerous studies demonstrate the involvement of GR in AD, particularly via the increase of Aβ production and the hyperphosphorylation of Tau. In an acute model of AD (icv injection of an oligomeric solution of oAβ25-35 peptides in rat), we observed a dysregulation of the HPA axis, associated with a set of cellular alterations reminiscent of the human pathophysiology. There is a vicious cycle in which the pathology induces an overproduction of GC, which in turn potentiates AD. The objective of my thesis was therefore to break this vicious cycle using a new class of molecules acting as selective GR modulators (sGRm). The sGRm have the particularity to abrogate the pathological effects of GR, while retaining their physiological signaling. In a first study, we showed in the oAβ25-35 model that a sGRm (CORT113176) reverses in the hippocampus all the alterations induced by amyloid toxicity (short-term memory deficits, high plasma GC levels, synaptic deficits, neuroinflammation, apoptosis and increased Aβ synthesis). In a second study, we performed analyzes in the prefrontal cortex. This structure of interest in AD is also very rich in GR, suggesting that this region is very sensitive to deregulation of the HPA axis. Here, we used sGRm as a tool to characterize the involvement of GR in a number of intracellular signaling pathways. We notably observed the GR phosphorylation state, their chaperones (HSP90 / 70), the balance between the amyloidogenic and non-amyloidogenic pathways or the main enzymes involved both in GR and Tau phosphorylation (GSK-3β , Cdk5, Calpain-1, Fyn). GR appeared to be involved in numerous processes associated with oAβ25-35 toxicity, and CORT113176 reversed this toxicity, highlighting the central role played by GR in the pathophysiology of AD. In a final study, following all of these initial results, and in order to validate the therapeutic potential of CORT113176, we tried to bring the proof of concept via two complementary approaches. Firstly, we tested the robustness of the treatment with the sGRm in the oAβ25-35 model in order to observe whether breaking the vicious circle by restoring the physiology of the HPA axis, the GC and the GR could help at long-term to fight against the pathology. The first results showed that CORT113176 reversed at long-term the amyloid toxicity on the parameters measured previously, but also seems to reverse Tau hyperphosphorylation. Finally, we wanted to confirm the therapeutic interest of breaking the vicious circle in a transgenic mouse model of AD, the J20 mouse (mutated human APP transgene). In 9-month-old animals, CORT113176 again appeared to reverse a large number of markers associated with AD. All of these results place the HPA axis and GR at the heart of the pathophysiology of AD, which could make the link between amyloid toxicity and Tau hyperphosphorylation. This work also highlights the promising approach represented by sGRm which break the vicious circle between the deregulation of the HPA axis and amyloid toxicity, by restoring the primary role of GC and GR in the maintenance of homeostasis
Larangé, Alexandre. "Etude des mécanismes par lesquels les glucocorticoïdes régulent la maturation des cellules dendritiques humaines induite par des agonistes des récepteurs toll-like." Paris 11, 2008. http://www.theses.fr/2008PA114836.
During this work, we have highlighted the signaling pathways that are involved in human dendritic cell (dc) maturation, induced by imiquimod and 3m002, agonists of tlr7 and tlr8, respectively. Our results show that stat1/3 and p38mapk pathways are differentially involved in dc maturation induced by tlr7 or tlr8. Also, we have shown that glucocorticoids (gc) can inhibit dc maturation induced by these two agonists. Indeed, gc selectively inhibit jnk activation by inducing mkp-1 expession. However, the use of mkp-1 sirna revealed that this phosphatase is only slightly involved in the inhibitory effect of gc on imiquimod-induced dc maturation, and does not participate in the inhibitory effect of gc on 3m002-induced dc maturation. Moreover, we have highlighted the induction of socs1 protein by gc in dc
Turrel, Marie-Odile. "Caractérisation des récepteurs aux glucocorticoïdes dans la glande mammaire fœtale, néonatale et tumorale de rate." Besançon, 1986. http://www.theses.fr/1986BESA2028.
Blicq, Stéphane. "L'effet des maléimides N-substituées sur la transformation du récepteur des hormones glucocorticoïdes du cytosol de foie de rat." Lille 1, 1987. http://www.theses.fr/1987LIL10037.
Grino, Michel. "Caractérisation et régulation par les glucocorticoïdes des récepteurs antéhypophysaires du corticotropin-releasing factor chez le rat et chez l'homme." Aix-Marseille 2, 1989. http://www.theses.fr/1989AIX22046.
Berthiaume, Magalie. "Contribution des glucocorticoïdes aux mécanismes d'action des récepteurs PPARgamma et leur implication dans le métabolisme lipidique." Thesis, Université Laval, 2007. http://www.theses.ulaval.ca/2007/24304/24304.pdf.
Kitchener, Pierre. "Régulation intracellulaire de l'activité du récepteur aux glucocorticoi͏̈des (GR) in vivo." Bordeaux 2, 2003. http://www.theses.fr/2003BOR21081.
The aim of this work was to determine how important are the mechanisms regulating glucocorticoids effects on the central nervous system. We measured GR nuclear translocation and their binding to specific GRE sequences during the circadian cycle and in response to an acute stress. We then undertook the same measurements in 2 rat models more prone to self administer drugs of abuse. GR activity in physiological conditions is variable among cerebral structures and tissues, and is rather submitted to many structure dependent regulations. Moreover, rats more vulnerable to drugs of abuse show less GR activation in structures involved in the negative feedback on the HPA axis while having more activation in the nucleus accumbens, one of the main neurobiological substrate of the motivational effects of drugs. This work shows how important intracellular regulations of GR activity are on the physiological and pathophysiological effects of glucocorticoids on the central nervous system and behaviour
Ganti, Krishna Priya. "Transcriptional control of expression of the thymic stromal lymphopoietin (TSLP) gene." Strasbourg, 2010. https://publication-theses.unistra.fr/public/theses_doctorat/2010/GANTI_Krishna_Priya_2010.pdf.
Thymic stromal lymphopoietin (TSLP), the master regulator of allergic inflammation, is highly expressed in human atopic dermatitis (AD) skin lesions, and several lines of evidence have demonstrated that TSLP expression is both necessary and sufficient to induce atopic inflammation in mouse. Previous studies from our laboratory have suggested that Nuclear Receptors (NRs) RXRα, RXRβ, VDR and RAR may be differentially regulating the expression of TSLP in mouse epidermis, depending on the stimulus. My thesis work experimentally demonstrates that, under physiological conditions, TSLP promoter remains repressed by the unliganded NR heterodimers, VDR/RXRα and/or RARγ/(RARα)/RXRβ. This repression can be relieved by release of unliganded NR heterodimers as well as by activation with agonistic ligands of VDR and/or RARγ. Further, I have characterized binding elements for NFĸB, AP1, STAT, and Smad transcription factors, which can function independent of the presence of the above NR repressor complexes. As Glucocorticoids (GCs) are important tools for AD treatment, I have also investigated whether they act by repressing TSLP expression. In the process of analyzing GC-mediated transcriptional repression of TSLP, I have discovered a mechanism of GC-induced direct transrepression, which is mediated through the direct binding of Glucocorticoid Receptor (GR) to a “simple” evolutionary-conserved cis-acting negative response element (IR nGRE). Conserved IR nGREs are present in >1000 mouse/human orthologues genes, which can be repressed by GCs in vivo
Berthiaume, Magalie. "Contribution des glucocorticoïdes aux mécanismes d'action des récepteurs PPAR[gamma] et leur implication dans le métabolisme lipidique." Doctoral thesis, Université Laval, 2007. http://hdl.handle.net/20.500.11794/18891.
Aouizerate, Bruno. "Hormones glucocorticoïdes et vulnérabilité aux drogues d'abus : rôle des récepteurs aux corticostéroïdes de type II (ou glucocorticoi͏̈des)." Bordeaux 2, 2000. http://www.theses.fr/2000BOR28746.
Marissal-Arvy, Nathalie. "Différences fonctionnelles au niveau des récepteurs aux corticostéroi͏̈des entre les souches de rats Brown Norway et Fischer 344 : Recherche de leurs mécanismes moléculaires." Bordeaux 2, 2001. http://www.theses.fr/2001BOR28862.
Comparative studies of inbred rat strains differing in their reactivity to stress are used to investigate genetic mechanisms of variations in adrenocortical axis function. Compared to Fischer 344 (F344) rats, Brown Norway (BN) rats secrete less corticosterone during the dark phase of the diurnal cycle and during recovery from restraint stress. Such differences in mineralocorticoid (MR) and glucocorticoid (GR) receptors between BN and F344 strains. This study aimed to investigate molecular mechanisms involved in these differences. The first experiments were designed to compare the effects of hormone deprivation by adrenalectomy (ADX) and of treatments with corticosterone or MR (DOC) and GR (RU28362) specific ligands on some parameters modulated by these receptors. ADX had no effect on body weight or fluid intake in BN rats, suggesting tgat MR is constitutively active, i. E. Active independently of the presence of its ligands, in the BN strain. On the other hand, treatments with corticosterone or RU28362 induced greater effects in BN than in F344 rats, suggesting a greater efficiency of GR-mediated mechanisms in BN rats. Molecular approaches revealed a point mutation in the N-terminal part of the BN MR, and showed a strong genetic linkage between the MR locus and insensitivity of BN rats to ADX. The genome scan with microsatellite markers of rats of the second generation born from the BNxF344 crossbreeding showed a QTL in the MR region, but also other QTLs, notably in a genomic region containing two MR renal targets. The hyperefficiency of GR showed in BN rats is essentially determined by a region on chromosome 1
Nevoux, Jérôme. "Régulation hormonale de la sécretion d'endolymphe : Implications dans la maladie de Menière." Paris 7, 2014. http://www.theses.fr/2014PA077221.
The Menière's disease is a frequent and incapacitating pathology associating vertigo, deafness and tinnitus, characterized by crisis triggered by stress. This is associated with a dilation of the endolymphatic compartment of the inner ear, so-called endolymphatic hydrops. The original composition of the endolymph (rich in k+), an inner ear liquid, has to be tightly regulated to insure the proper ear function. The aim of this thesis was to better characterize the regulation of the endolymph composition and volume by the stress hormones and to envision new therapeutic strategies for the menière's disease. The regulation of the k+ secretion by the stress hormones (catecholamines and avp) was studied in the endolymph secreting cells, the ec5v cells originating from transgenic mouse vestibule. We demonstrated that these hormones stimulate k+ secretion and could play a prominent role in triggering crisis of the menière's disease. The water transport and aquaporins (aqp) expression were studied under glucocorticoids stimulation in ec5v cells, in human utricular cells and in mice. We demonstrated that dexamethasone stimulate the aqp3 expression in these models, via a glucocorticoid receptor-mediated transcriptional mechanism. Dexamethasone stimulates the vectorial water transport from apical to basolateral side of vestibular ec5v cells. We proposed that glucocorticoids could be used as a therapeutic option to enhance water reabsorption and thus decrease the pressure applied onto neurosensorial cells
Danze, Pierre Marie. "Le récepteur des glucocorticoi͏̈des : un facteur de transcription dont l'activité de liaison spécifique à l'ADN est régulée par le ligand stéroi͏̈den." Lille 1, 1989. http://www.theses.fr/1989LIL10142.
Charbonneau, Chantal. "Implication du système sérotoninergique sur l'expression du gène des récepteurs aux glucocorticoïdes dans le mode d'action de l'antidépresseur fluoxétine." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0002/MQ43796.pdf.
Sainte-Marie, Yannis. "Rôle physiopathologique du récepteur minéralocorticoïde dans le coeur et la peau : comparaison avec le rôle du récepteur glucocorticoïde." Paris 7, 2006. http://www.theses.fr/2006PA077162.
Mineralocorticoïd (MR) and glucocorticoïd receptors (GR) are closely related nuclear receptors. Their overlapping expression pattern and their common target gene in vitro lead us to question their respective effects in vivo. We use conditional transgenic models to overexpressed MR or GR in cardiomyocytes or in keratinocytes and to study receptors' actions. MR overexpression in cardiomyocyte increases L-type calcium and decreases transient outward potassium currents leading to action potential duration lengthening. This ionic current remodeling leads to ventricular arrhythmia. GR overexpression induces the same currents modifications and moreover a decrease in sodium and slowly inactivating potassium currents. These modifications lead to severe cardiac conduction defect but not to ventricular arrhythmia. MR and GR overexpression models and a previously generated MR downexpression model were used to study by microarray the target genes of the receptors. MR overexpression in keratinocytes leads to epidermal hypotrophy and alopecia with appearance of kystic follicle. This phenotype is close to the one describe for GR overexpression model. This work points to new physiopathological roles of MR and GR. Comparison of MR and GF overexpression induced phenotype suggests overlapping as well as specific effects of the receptors
Ueberschlag-Pitiot, Vanessa. "Régulation des fonctions musculaires par les glucocorticoïdes et les androgènes." Thesis, Strasbourg, 2016. http://www.theses.fr/2016STRAJ041/document.
The use of glucocorticoids (GC) to treat inflammatory diseases or androgen antagonists for prostate cancer is limited by the occurrence of side effects such as muscle atrophy. As the underlying mechanisms were unclear, we characterized the effects of GC and androgens on muscle mass and function. Our results demonstrate that myofiber GC receptor negatively controls muscle mass by distinct actions under physiological and pharmacological levels of GC. Moreover, our data identified many genes and networks controlled by GC in myofibers. We also showed that androgens promote the gain in muscle performance during postnatal development via the improvement of specific maximal force and power. Thus, this study allowed to clarify the molecular and cellular mechanisms regulating muscle homeostasis, and paves the way to identify new therapeutic targets
Pinheiro, do nascimento Ludmila. "Stratégies de ciblage des macrophages alvéolaires pour l’administration de glucocorticoïdes." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS215.
This work focuses on strategies to target glucocorticoids to alveolar macrophages. We have synthesized a budesonide prodrug, budesonide palmitate (BP), increasing its lipophilicity to extend drug half-life in the lungs. BP PEGylated nanoparticles were developed and studied to obtain a stable formulation with suitable physicochemical characteristics and high drug loading to enter alveolar macrophages, key players in lung inflammation. In vitro tests on RAW 264.7 macrophages confirmed the anti-inflammatory activity and absence of cytotoxicity of nanoparticles. These were then encapsulated into Trojan microparticles obtained by spray-drying to facilitate their delivery to the lung as dry powders and release nanoparticles directly to the pulmonary alveoli. Spherical hollow microparticles containing from 0 % to 20 % of BP nanoparticles presented suitable aerodynamic diameters and fine particle fraction for lung delivery. In vivo pharmacokinetic studies demonstrated high and extended budesonide concentrations in the lungs, with low plasma concentrations. In the second part of this thesis, another macrophage targeting strategy was assessed by decoration of nanoparticle surface with mannose. After synthesis of a mannosylated lipid, nanoparticles were formulated and characterized, demonstrating high drug loading and stability up to 30 days. In vitro tests on RAW 264.7 macrophages showed that the presence of mannose on the surface increases nanoparticles internalization 2 fold after 48 h incubation, as compared with PEGylated nanoparticles
Mansart, Arnaud. "Actions et mécanismes d'actions cardio-vasculaires des glucocorticoïdes dans un modèle expérimental de choc septique chez le rat." Nancy 1, 2002. http://www.theses.fr/2002NAN11322.
El, Ayachi Soulaf. "Etude de la régulation de la synthèse du PAI-1 [plasminogène de type 1] et de son rôle au cours de l'obésité." Aix-Marseille 2, 2006. http://www.theses.fr/2006AIX20703.
Auclair, Vincent Sacha. "Étude de la régulation des gènes CYP2B par les inducteurs de type phénobarbital, comprenant la mise à l'épreuve du modèle actuel." Thesis, Université Laval, 2009. http://www.theses.ulaval.ca/2009/26471/26471.pdf.
Faraj, Hassane. "Synthèse en série 19-nor de nouvelles spirolactones 11bêta substituées : étude de l'influence de la substitution en position 11bêta sur l'affinité pour le récepteur minéralocorticoi͏̈de." Montpellier 2, 1991. http://www.theses.fr/1991MON20253.
Le, billan Florian. "Identification et régulation transcriptionnelle des gènes cibles du récepteur des minéralocorticoïdes dans les cellules rénales." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS277.
The mineralocorticoid receptor (MR), activated by aldosterone, exhibits numerous pleiotropic functions, most notably at the renal level where it regulates electrolytic homeostasis. Dysfunctions in the mineralocorticoid signaling pathway are involved in major diseases in Human. During this work, we have identified by ChIP sequencing the first MR cistrome in a human renal cell lineage. The characterization of the identified genomic targets allowed us to define a specific MR responsive element, and to demonstrate the existence of two transactivation processes for MR: through direct binding to DNA or through indirect interaction via binding to other transcription factors. MR is physiologically confronted with a duality with the glucocorticoid receptor (GR), since they share a common ligand, cortisol, and some of their genomic targets, whose PER1 gene. On the latter, MR and GR are distinguished by different dynamic and cyclical recruitment, varying according to hormone, and coordinated with the one of transcriptional partners, translating into the regulation of short-term and long-term effects. Finally, by serial and tandem ChIP experiment, we have demonstrated that MR and GR act as homodimer and as heterodimer.Identification of new MR genomic targets and characterization of its molecular mechanisms of action, improve our understanding of the pathophysiology of the mineralocorticoid signaling pathway. This could ultimately, notably through the development of selective MR antagonists like Finerenone, lead to new therapeutic strategies
Brossaud, Julie. "Modulation pré et post-récepteur de l’exposition aux glucocorticoïdes : rôles du diabète de type 1 et de la vitamine A." Thesis, Bordeaux 2, 2013. http://www.theses.fr/2013BOR22081/document.
Rôles to mobilize body resources and to adapt to endogenous or exogenous changes that might disrupt the homeostasis of the body. Nutritional & metabolic factors may modify the intensity of GC action in: i) the activation of the corticotrope axis and their secretion by the adrenals, ii) their bioavailability ("pre-receptor" regulation), iii) the transcriptional activation of their receptors ("post-receptor" regulation). The main target of this work is to explore the role of some metabolic/nutritional endogenous or exogenous factors in modulating pre- and post-receptor action of GC. Our attention first focused on the role of diabetes and the related inflammation in patients with type I diabetes, and pre-receptor metabolism of cortisol. We showed that a significant increase in the activity of hydroxysteroid dehydrogenase 1, the main enzyme of intracellular cortisol regeneration, is correlated with markers of inflammation in diabetic children. This suggests a link between diabetes and the low-level chronic inflammation and increased cellular exposure to GC . Then, we focused on the action of all-trans retinoic acid (atRA), the active metabolite of vitamin A on the transcriptional activity of GC. We used an in vitro model of hippocampal cells as GC and atRA have contrasted effects on mnesic processes in vivo. We observed a transcriptional interaction between the GC and retinoic pathways targeting their receptors and genes involved in neuronal plasticity. atRA also affects the phosphorylation of the GC receptor and modifies its transcriptional activity. Lastly, both atRA and GC affect cellular organisation of actin cytoskeleton. The knowledge acquired by studying the action of nutritional molecules on GC action could be used to easily reduce the deleterious effects of GC in chronic stress. Clinical studies have started in this direction
Ben, Simon Elsa. "Pathologie moléculaire des déficits secondaires isolés en glucocorticoïdes chez l'homme : étude de deux gènes candidats : POMC et récepteur de la CRH." Lyon 1, 2002. http://www.theses.fr/2002LYO1T112.
Drocourt, Lionel. "Régulation de l'expression des cytochromes P450 des sous-familles 2B, 2C et 3A dans l'hépatocyte humain : rôles physiologiques et pharmacologiques des récepteurs nucléaires GR, PXR, et VDR." Montpellier 2, 2001. http://www.theses.fr/2001MON20203.
Besnault, Pierre. "Impact pathologique du stress chronique dans la maladie de Parkinson : rôle des récepteurs aux glucocorticoïdes dans la régulation des organelles de signalisation immunitaire innée." Electronic Thesis or Diss., Sorbonne université, 2023. http://www.theses.fr/2023SORUS534.
This project focuses on the pathological consequences of chronic stress (CS) and the alteration of signaling mediated by glucocorticoids (GCs) and their receptors (GRs) in Parkinson's disease (PD). Stress stimulates the hypothalamic-pituitary-adrenal (HPA) axis and the secretion of GCs that triggers a large number of physiological responses which are beneficial in the short term. On the other hand, CS disrupts the HPA axis, alters these physiological responses and leads to the development of neuropsychiatric disorders such as depression, a known risk factor for PD. In line with this, evidence suggests that the HPA axis is altered in PD patients together with a central alteration of GC/GR signaling. How could these alterations impact the pathomechanisms and contribute to disease progression? PD is an uncurable neurological disorder of still unknown origin. Sporadic form of the disease represents a very large majority of PD cases, and probably results from complex interactions between genetic and environmental risk factors. Clinically, PD is diagnosed upon identification of motor symptoms resulting from a massive loss of dopaminergic neurons in the substantia nigra. Neurodegeneration is associated with the aggregation of alpha-synuclein (aSyn) that deposits into intraneuronal inclusions known as Lewy bodies and neurites. Associated with neurodegeneration, immune responses orchestrating inflammatory processes are mounted and likely involved in disease progression. In the past years, one of the greatest finding regarding the mechanism of immune cell activation in PD has been the discovery of the structural properties of aSyn assemblies being able to act as true pathogen-associated molecular pattern, and to mediate the activation of supramolecular organizing centers (SMOCs), which are considered as important innate immune signaling platforms. Given that one of the major properties of GR is to regulate inflammatory response in immune cells, we hypothesize that chronic stress-mediated HPA axis and GC/GR signaling alterations could exacerbate inflammatory responses through an overactivation of SMOC-dependent signaling. Our work shows that CS not only alters microglial GC/GR signaling, but also increases neuronal death and microglia-associated inflammatory response in a mouse model of PD. Understanding precisely the link between the alteration of GC/GR signaling and the increase in the inflammatory response by focusing on SMOC-dependent signaling will allow us to better understand the different pathophysiological molecular mechanisms, but also identify new therapeutic targets
Jaffuel, Dany. "Corticothérapie et asthme : étude cellulaire de la transrépression du facteur de transcription AP-1 par le récepteur aux glucocorticoi͏̈des." Montpellier 1, 1997. http://www.theses.fr/1997MON11104.
Compagnion, Anne-Claire. "Étude moléculaire de l'inflammation chronique dans la maladie de Parkinson TLR9 activation via microglial glucocorticoid receptors contributes to degeneration of midbrain dopamine neurons Glucocorticoid receptor in astrocytes regulates midbrain dopamineneurodegeneration through connexin hemichannel activity." Thesis, Sorbonne université, 2019. http://www.theses.fr/2019SORUS515.
Lewy bodies, composed of α-synuclein (αSyn) aggregates, are intraneuronal inclusions that characterize a group of pathologies called α-synucleinopathies, of which Parkinson's disease (PD) is the most common. It is believed that distinct pathological characteristics of these α-synucleinopathies could arise from existence of different assemblies of αSyn proteins, or "strains". In PD, chronically activated glial cells contribute to the loss dopaminergic neurons (DN) in substantia nigra (SN), a major feature of PD. But the role of glia in the toxicity induced by different strains of αSyn is unknown.During my thesis, I found a differential impact of 2 strains of αSyn-fibril and ribbon-on DN degeneration and glial reactivity in vivo. My results showed greater neurotoxicity of αSyn-fibril strain towards DN, which also maintain a chronic inflammatory state in SN. In primary microglial cells, the 2 strains exhibited differential clearance and inflammatory responses providing further insights into how αSyn strains can participate in different pathological outcomes. Glucocorticoids (GC) is a potent regulator of inflammation acting through its receptor GR. We showed decreased microglial and astrocytic GR expression in the SN of PD, suggesting the dysfunction of GC-GR system could paly a role in chronic inflammation. Using mice lacking GR in microglia or astrocytes, I showed the protective effect of glial GR on αSyn-induced DN death. Two mechanisms of GR dysfunction were identified in these studies: TLR9 activation in microglia and connexin 43 hemichannel activity in astrocytes, both of which regulate DN death in SN
Maatouk, Layal. "Glial glucocorticoid geceptors in parkinsonism." Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066302.
Chronic inflammation, mounted by activated glia, contributes to dopamine neuron (DN) loss, a major hallmark of Parkinson’s disease. It can be postulated that the extent of DN injury inflicted by inflammation is affected by the efficacy of regulatory mechanisms. The activation of hypothalamic–pituitary–adrenal axis results in release of glucocorticoids, which activate glucocorticoid receptor (GR). GR exerts adaptive responses including resolution of inflammation to restore the homeostatic state. We previously demonstrated the role of microglial GR in regulating the intensity and duration of inflammation, which influences DN survival. My thesis was centered on dissecting the roles of microglial and astrocytic GR during DN degeneration in experimental Parkinsonism. In the first part of my thesis, we conducted comparative transcriptome experiments of ex vivo microglia acutely isolated from mice treated with MPTP (model of parkinsonism) and identified genes and pathways in microglia regulated by GR, potentially involved in chronic inflammation in PD. In the second part of my thesis, we found that microglial GR regulates Toll-Like Receptor 9-induced DN loss by regulating the lysosomal compartment and demonstrated that diminished sensitivity of GR in microglia creates a permissive environment for TLR9 activation by endogenous mitochondrial DNA to become lethal for DNs. In the third part of my work, we showed that during DN degeneration, astrocytic GR regulates inflammatory gene expression and prevents connexin-43 hemichannel activity that contributes to DN loss. Overall, both microglial and astrocytic GR play essential roles in regulating chronic and acute inflammation
Dalle, Heloïse. "Rôle du récepteur adipocytaire des glucocorticoïdes dans les troubles métaboliques liés à un traitement par la corticostérone Adipocyte glucocorticoid receptor deficiency promotes adipose tissue expandability and improves the metabolic profile under corticosterone exposure Glucocorticoid-induced insulin resistance is related to macrophage visceral adipose tissue infiltration." Thesis, Sorbonne université, 2019. https://accesdistant.sorbonne-universite.fr/login?url=http://theses-intra.upmc.fr/modules/resources/download/theses/2019SORUS065.pdf.
Glucocorticoids (GC) are among the medications most commonly prescribed because of their anti-inflammatory and immunosuppressive properties. However, high doses can lead to side effects including GC-induced diabetes and lipodystrophy. The contribution of adipocyte glucocorticoid receptor (GR) in the molecular mechanisms of these complications remains to be investigated. The goal of this study was to determine the precise role of the GR in the development of insulin-resistance and associated metabolic dysregulations in a context of hypercorticism. For this purpose, we have generated an inducible mouse model of GR invalidation specifically in the adipocyte (AdipoGR-KO), which was submitted to a four-week corticosterone treatment. Metabolic phenotype of AdipoGR-KO mice showed an increase of fat mass associated with a paradoxical improvement of glucose tolerance, insulin sensitivity, lipid profile and liver steatosis compared to WT mice. Preferential and beneficial fat storage in adipose tissue prompted us to investigate the mechanisms involved in the excessive development of adipose tissue, in particular the vascularization. Surprisingly, our results showed a higher development of capillary network in fat pads of AdipoGR-KO mice, associated with a strong induction of the angiogenic factor VEGF-A and its transcriptional regulator HIF-1α. Thus, we show for the first time that GR could be a limiting factor of adipose tissue expansion through the inhibition of the angiogenic process
Boivin, Audrey. "Rôle des récepteurs Toll-like dans la régénérescence d'axones périphériques lésés : iImpacts sur la dégénérescence Wallérienne et la récupération des fonctions locomotrices." Master's thesis, Université Laval, 2007. http://hdl.handle.net/20.500.11794/19483.
Trayer, Vincent. "Rôle du cortisol dans le développement des ionocytes de la peau chez l'embryon de médaka (Oryzias Latipes) et conséquences sur l'osmorégulation des stades larvaires." Thesis, Rennes 1, 2013. http://www.theses.fr/2013REN1S144/document.
Cortisol is a key hormone regulating in teleost fish water and ionic homeostasis in freshwater and seawater and in acclimation during salinity changes. However, its role during embryonic stages is still poorly known, especially its involvement in the development of ionic transport specialized cell, namely the ionocytes. The aim of my thesis was to determine cortisol involvement in epidermal ionocyte lineage establishment in medaka (Orysias latipes) embryos and to study consequences of cortisol elevation in medaka embryos on larval osmoregulatory abilities during transfer from freshwater to ion-poor environment or to seawater transfer. In a first part, we studied the dynamic of ionocyte appearance in yolk-sac epithelium of embryos. Ionocytes appear in two distinct waves with their own kinetic. This allowed us to propose a model of ionocyte development for each wave. In the continuity of this first part, we have showed that exogenous cortisol doesn’t modify the proliferation and/or differentiation rate of epidermal ionocytes but rather accelerate their differentiation. In addition, we have identified GR2, one of glucocorticoid receptors, as the main regulator of ionocyte ontogenesis, most likely through its maternal transcripts. Finally, we have showed that medaka larvae are able to quickly regulate their Na+ and Cl- ion contents after hypo- or hyper-osmotic challenges. In contrast, larvae ability to regulate Ca2+ ion contents is more limited during hypo-osmotic challenge. A doubt on the effectiveness of the cortisol treatment, in this last part, prevent us to understand the relationship between cortisol role in ionocyte ontogenesis and its osmoregulatory functions after hatching. These studies have established in medaka the basis of embryonic ionocyte ontogenesis and larval osmoregulation in order to clarify the role of cortisol and its receptors. Similarly, this fish model could be used as a support for identification and characterization of new regulators of the osmoregulation function
BENATMANE, SAMIA. "Effets d'un choc thermique modéré sur le fonctionnement des récepteurs hormonaux lors du contrôle par les glucocorticoïdes de la réponse glycogénique a l'insuline dans l'hépatocyte fœtal en culture." Paris 7, 1996. http://www.theses.fr/1996PA07GA03.
Roumestan, Caroline. "Mesure des activités transcriptionnelles des glucocorticoi͏̈des et caractérisation des effets anti-inflammatoires des antihistaminiques H1 et des antidépresseurs : implication pour le traitement de l'asthme." Montpellier 1, 2004. http://www.theses.fr/2004MON1T011.