Bifidobacterium longum and Lactobacillus helveticus Synergistically Suppress Stress-related Visceral Hypersensitivity Through Hypothalamic-Pituitary-Adrenal Axis Modulation

BACKGROUND/AIMS: Visceral pain and hypothalamic-pituitary-adrenal axis (HPA) dysregulation is a common characteristic in irritable bowel syndrome (IBS) patients. Previously, we reported that a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) prevents chronic stress-mediated brain function abnormalities by attenuating the HPA axis response. Here, we compared the effect between different probiotic treatments on the perception of visceral pain during colorectal distension (CRD) following a chronic stress and the consequences to the activity of the HPA axis. METHODS: After a 2-week treatment with a combined probiotic formulation, or L. helveticus or B. longum alone in stressed mice, the visceral pain in response to CRD was recorded. The expression of glucocorticoid receptors was determined in the different brain areas involved in the stress response (hypothalamus, hippocampus, and prefrontal cortex). The plasma levels of stress hormones were also measured. RESULTS: A pretreatment using the combination of probiotic formulation significantly reduces the chronic stress-induced visceral hypersensitivity respectively at 0.06, 0.08, and 0.10 mL CRD volume. However, a single probiotic (B. longum or L. helveticus) administration is less effective in reducing visceral pain in stressed mice. Moreover, the expression of the glucocorticoid receptor mRNA was consistently up-regulated in several brain areas after pretreatment with a combined probiotic, which correlated with the normalization of stress response compared to the inconsistent effects of a single probiotic. CONCLUSION: The combination of L. helveticus and B. longum is more effective in regulating glucocorticoid negative feedback on the HPA axis than probiotic alone and subsequently in treating stress-induced visceral pain.

Efectos de la inactivación sistémica de los receptores GR y MR sobre el daño rápido en la recuperación de la memoria espacial inducido por corticosterona / Systemic Inactivation of GR and MR Receptors on Corticosterone-induced rapid damage in Spatial Memory Recovery

Estudios previos de nuestro laboratorio han mostrado que diez minutos después de la administración sistémica de corticosterona se dificulta la recuperación de la memoria espacial en el laberinto de Barnes, sin embargo se desconocen los mecanismos que subyacen a este efecto. Dado que los glucocorticoides ejercen sus acciones a través de los receptores de tipo GR y MR, en el presente estudio se evaluó la participación de estos receptores en el efecto perjudicial rápido de la corticosterona sobre la memoria espacial. Para ello 37 ratas Wistar macho fueron entrenadas en la tarea y 24h después recibieron una inyección subcutánea de antagonista GR, antagonista MR o vehículo. 50min después los animales fueron inyectados con corticosterona o vehículo por vía intraperitoneal y 10min después se evaluó la recuperación de la memoria espacial. Los resultados mostraron que la corticosterona perjudicó rápidamente la recuperación de la memoria espacial a largo plazo, pues los animales inyectados con esta hormona presentaron mayores latencias de escape, mayor número de errores, mayor número de exploraciones y mayor distancia recorrida hasta alcanzar la meta; un efecto revertido solamente con la administración del antagonista MR. Este hallazgo concuerda con estudios in vitro donde se muestra que los efectos rápidos de la corticosterona sobre la trasmisión glutamatérgica en el hipocampo están mediados por los receptores MR.

Previous studies of our laboratory have shown that it is difficult to recover the spatial memory in the Barnes maze ten minutes after a systemic administration of corticosterone; however the mechanisms that underlie this effect are unknown. Considering glucocorticoids exert their actions through GR and MR type receptors, the present study evaluated the participation of these receptors in the rapid damaging effect of corticosterone on spatial memory. For this, 37 male Wistar rats were trained on the task and 24 h afterwards they received a subcutaneous injection of GR antagonist, MR antagonist or vehicle. 50 min later the animals were injected with corticosterone or vehicle intraperitoneally and 10 min later, the spatial memory recovery was evaluated. The results indicated that corticosterone rapidly impaired spatial long-term memory recovery, as animals injected with this hormone presented higher escape latencies, more errors, higher exploration and greater traveled distance to reach the goal; an effect reverted only with the administration of the MR antagonist. This finding agrees with in vitro studies showing that the rapid effects of corticosterone on glutamatergic transmission in the hippocampus are mediated by MR receptors.

Topical corticosteroids in dermatology.

Since their introduction, topical corticosteroids have become indispensable in the treatment of various dermatoses. Hydrocortisone was the fi rst compound. Modifi cations in the basic structure generated in vivo activity and thus different topically active compounds were discovered. Apart from the Stoughton vasoconstrictor assay, various other methods are used for potency assessment of topical corticosteroids. Topical corticosteroides are classifi ed based upon potency and action of these molecules. Mechanism of action at the cellular level and indications of topical corticosteroid use have been discussed. Various adverse effects often occur as an extension of their activity combined with inappropriate usage. Tachyphylaxis and contact allergy are potential problems in clinical practice. Newer compounds with improved risk-benefit ratio are available.

Characteristics and significance of interferon-induced protein with tetratricopetide repeats 1 expressed in radia-tion injury and infection stress / 局解手术学杂志

Objective To explore characteristics and significance of interferon-induced protein with tetratricopetide repeats 1 expressed in radiation injury and infection stress.Methods RNA was extracted from Raw264.7 cell,3T3 cell and 10T1 /2 cell after 5 hours stimulated with 5 μg/mL LPS.At the same time,to set up normal control group (untreated by LPS),and RNA of IFIT1 was detected by RT-PCR.Total-ly 20 C57 /BL6 mice were randomly divided into 4 groups,namely 0 h group,1 h group,4 h group and 12 h group.The mice were given 12 Gray60Co full-body exposure once,then liver IFIT1 was detected by western blot.Results Stimulated with LPS for 5 hours,IFIT1 was in-duced expression in Raw264.7 cell,3T3 cell and 10T1 /2 cell.The expression of normal control group was negative.The level of IFIT1 /Actin increased significantly 1 hour after radiation injury,and it reached the peak 12 hours after radiation injury (P <0.01).Conclusion LPS can stimulated a variety of cell lines expressed IFIT1,prompting that IFIT1 may participate in the occurrence and development of post-traumatic toxemia.IFIT1 of liver tissue increased significantly during the early stage in radiation mice.

Selective Activator of the Glucocorticoid Receptor Compound A Dissociates Therapeutic and Atrophogenic Effects of Glucocorticoid Receptor Signaling in Skin

BACKGROUND: Glucocorticoids are effective anti-inflammatory drugs widely used in dermatology and for the treatment of blood cancer patients. Unfortunately, chronic treatment with glucocorticoids results in serious metabolic and atrophogenic adverse effects including skin atrophy. Glucocorticoids act via the glucocorticoid receptor (GR), a transcription factor that causes either gene transactivation (TA) or transrepression (TR). Compound A (CpdA), a novel non-steroidal GR ligand, does not promote GR dimerization and TA, retains anti-inflammatory potential but induces fewer metabolic side effects compared to classical glucocorticoids when used systemically. As topical effects of CpdA have not been well studied, this work goal was to compare the anti-inflammatory and side effects of topical CpdA and glucocorticoids and to assess their effect on GR TA and TR in keratinocytes. METHODS: We used murine immortalized keratinocytes and F1 C57BlxDBA mice. Effect of glucocorticoid fluocinolone acetonide (FA) and CpdA on gene expression in keratinocytes in vitro and in vivo was evaluated by reverse transcription-PCR. The anti-inflammatory effects were assessed in the model of tumor promoter 12-O-tertradecanoyl-acetate (TPA)-induced dermatitis and in croton oil-induced ear edema test. Skin atrophy was assessed by analysis of epidermal thickness, keratinocyte proliferation, subcutaneous adipose hypoplasia, and dermal changes after chronic treatment with FA and CpdA. RESULTS: In mouse keratinocytes in vitro and in vivo, CpdA did not activate GR-dependent genes but mimicked closely the inhibitory effect of glucocorticoid FA on the expression of inflammatory cytokines and matrix metalloproteinases. When applied topically, CpdA inhibited TPA-induced skin inflammation and hyperplasia. Unlike glucocorticoids, CpdA itself did not induce skin atrophy which correlated with lack of induction of atrophogene regulated in development and DNA damage response 1 (REDD1) causatively involved in skin and muscle steroid-induced atrophy. CONCLUSIONS: Overall, our results suggest that CpdA and its derivatives represent novel promising class of anti-inflammatory compounds with reduced topical side effects.

Ginsenoside metabolites Compound K suppress TNF-α-induced RANTES secretion in human bronchial epithelial cell line / 第二军医大学学报

Objective To explore the effects of ginsenoside metabolite Compound K (CK) on TNF-α-induced RANTES secretion in human bronchial epithelial cell line BEAS-2B and to elucidate its possible mechanism. Methods BEAS-2B cells were cultured and treated with CK in different dosages, and then the secretion of RANTES in BEAS-2B cells exposed to inflammatory stimuli was measured by ELISA kits. Expressions of RANTES mRNA and protein were detected by RT-PCR and Western blotting analysis, respectively. Reporter gene assay was employed to elucidate the interaction between CK and activator protein 1(AP-1), glucocorticoid receptor (GR). CK antagonist mifepristone was used to observe whether the inhibitory effect of CK against RANTES was mediated by GR. Results TNF-α-induced secretion of RANTES in BEAS-2B was markedly inhibited by CK (3-30 μmol/L). Treatment with CK also reduced RANTES mRNA and protein expression. Reporter gene assays indicated that CK was a GR agonist and could repress TNF-α-induced AP-1 transactivation. The inhibitory effects of CK on RANTES secretion were antagonized by mifepristone, suggesting a pivotal role of GR. Conclusion These results suggest that CK may inhibit TNF-α-induced RANTES secretion in human bronchial epithelial cells, which might be associated with GR pathway activation and AP-1 pathway inhibition.

Relationship between hippocampal cortisol receptors and serum cortisol in aged depression rats / 中华老年医学杂志

Objective To observe the changes of behavior,blood cortisol level,glucocorticoid receptors (Grs) and mineralocorticoid receptors (MRs) in hippocampus area after four weeks of unpredictable chronic mild stress,and to investigate the probable role of hypothalamus-pituitary-adrenal (HPA) axis in the pathogenesis of depression in aged people.Methods Aged male Wister rats were randomly assigned to control group and model group.The model group received unpredictable mild stress,including food and water deprivation,restrain,tail clipping,forced swimming,white noise,cage titling and cage rotating for 4 weeks,while the control group was undisturbed unless routine feeding and cage changing.After 4 weeks of procedure,the behavior changes were assessed by sucrose intake test,open-field test and state evaluation,serum cortisol level was measured by chemiluminescent assay,the qualitation and quantitation of GRs and MRs in hippocampus area were evaluated by immunohistochemistry and Western blotting respectively.All data were analyzed by using t-test.Results Body weight,the grooming score,activities in openfield test,food intake and sucrose intake were decreased in model group as compared with control group after 2 weeks of chronic mild stress (all P＜0.01),suggesting the stress induced depressive-like behavior effects on aged rats.Serum cortisol level was elevated in model group as compared with control group after 4 weeks of chronic mild stress (P＜0.01).A decrease of the neurons was found in CA3 of hippocampus,but not in DG area.In CA3 area,GR positive neurons were decreased,but no significant decrease was found in MR positive neurons.Conclusions The chronic mild stress leading to depressive-like behavior effects in aged rats induces overall HPA axis dysfunction,elevation of serum cortisol level,impairment of hippocampus neurons and decrease of GR positive neurons.The HPA axis dysfunction induced by chronic mild stress may play an important role in the pathogenesis of depression.

Influence on Nasal Sinuses Mucosa Epithelium GR and IκBα Expression for Chronic Rhinosinusitis Model Treated with Bi-Yuan-Shu Oral Liquid / 世界科学技术-中医药现代化

This study was aimed to investigate the influence of Bi-Y uan-Shu (BYS) Oral Liquid on glucocorticoid re-ceptor (GR) and nuclear factor IκBα expression of nasal sinuses mucosa epithelium among chronic rhinosinusitis (CRS) models in order to explore its therapeutic mechanism for CRS from the anti-inflammatory reaction aspect. One hundred New Zealand rabbits were selected and randomly divided into the normal group, sham operation group, model group, BYS group, and clarithromycin group, with 20 rabbits in each group. After the CRS model was established, no intervention was given to the normal group, sham operation group, or model group. The intragastric administrations of BYS (1.5 mL·kg-1·d-1) and clarithromycin (25 mg·kg-1·d-1) were given for 14 days, respectively. The nasal sinuses mucosa was taken after the treatment. And HE stain was used to observe its pathological changes. Western Blotting was used in the detection of nasal sinuses mucosal epithelium cytoplasm GR and IκBα expression. The results showed that there were obvious nasal sinuses mucosa inflammatory cell infiltration, chronic inflammation changes, and obvious hyperplasia of glandular organs and goblet cells. Compared with the normal group, the GR expression was obviously reduced (P< 0.01). And the IκBα expression was obviously increased (P< 0.01). After the intragastric administration of BYS, the nasal sinuses mucosal epithelium was repaired with no obvious inflammatory cell infiltration, glandular organs, or goblet cells. Compared with the model group, the GR expression was obviously increased (P< 0.01). The IκBα expression was obviously decreased (P<0.01). It was concluded that BYS can promote GR expression to inhibit inflammation. Meanwhile, it can restrain IκBα expression to prevent the over inhabitation of IκBα on NF-κB. It can dynamically regulate the balance of the nasal sinuses mucosa epithelium inflammation.

Glucocorticoid receptor phosphorylation: The pathophysiological significance / 第二军医大学学报

Glucocorticoid (GC) has important physiological and pharmacological effects, which are mainly mediated by the GC receptor (GR). As a ligand-dependent transcriptional factor, GR activity is regulated by phosphorylation as well as GC; it is subject to hormone-dependent and -independent phosphorylation on several serine and threonine residues, especially in the N terminus. The GR is phosphorylated by cell-specific kinases such as cyclin-dependent kinases (CDKs), glycogen synthase kinase 3β (GSK3J7beta;) and mitogen-activated protein kinases (MAPKs). Phosphorylation regulates signaling and transcriptional activity of GR, thereby modulates the response of cells to GC and may be involved in the development and progression of diseases. Here we reviewed the recent research on GR phosphorylation and its pathophysiological significance.

Niveles sanguíneos de cortisol y receptores a glucocorticoides en hígado y placenta de cabras en diferentes etapas de la gestación / Blood levels of cortisol and glucocorticoid receptors in liver and placenta of goats at different stages of gestation

In order to analyze the temporal relationship between cortisol levels and glucocorticoid receptors (GR) in placenta and the possible influence in noninfectious abortion in goats, changes in GR in livers of the foetuses and mothers livers and in placenta together with foetal and maternal cortisol levels under stress conditions in non-pregnant (n = 5) and pregnant goats (n = 24) were recorded. The pregnant goats were five on days 40-50 of gestation (40-50 d), six on days 51-75, four on days 76-100, three on days 101-125, and six in more than 125 days of gestation. GR values in the placenta and maternal serum cortisol levels, measured by competitive binding methods, decreased from 10.4 ± 2.7 and 174.3 ± 59.1, in the group 40-50 d to 6.1 ± 2.3 fmol/mg of protein and 79.1 ± 66.1 nmol/l in the 76-100 d group, respectively. Values then increased, reaching the highest values (P ≤ 0.05) detected in this study (18.3 ± 2.7 and 659.6 ± 76.3) in the 101-125 d group followed by a decrease of 11.6 ± 2.1 fmol/mg protein and 231.6 ± 54.0 nmol/l in the +125 d group. Progesterone was bound competitively to placental GR. However, its binding values decreased in the 101-125 d group. Reciprocal profiles were found in maternal and fetal liver GR. These data suggest that goats have innate mechanisms for abortion that occurs in case of life-threatening conditions saving mother's life and giving opportunity for new pregnancies, allowing thus the survival of this species.

Para analizar la relación temporal entre los niveles de cortisol y los receptores a glucocorticoides (GR) en la placenta y su posible influencia en el aborto no infeccioso de las cabras, se registraron los cambios en el cortisol sanguíneo y en los GR del hígado de cabras adultas no gestantes (n = 5) y, además de los anteriores, en el hígado fetal y la placenta junto con los niveles de cortisol fetal de cabras gestantes (n = 24) bajo condiciones de estrés. Las cabras gestantes fueron: cinco de 40 a 50 días de gestación, seis de 51 a 75, cuatro de 76 a 100, tres de 101 a 125 y seis con más de 125 días de gestación. Los valores de GR en la placenta y los niveles de cortisol materno medidos por unión competitiva, decrecieron desde 10.4 ± 2.7 y 174.3 ± 59.1 en el grupo 40-50 d a 6.1 ± 2.3 fmol/mg proteína y 79.1 ± 66.1 nmol/l en el grupo 76-100 d, respectivamente. Ambos valores se incrementaron en el grupo 101-125 d, hasta alcanzar los más altos (P ≤ 0.05) detectados en este estudio (18.3 ± 2.7 y 659.6 ± 76.3) seguidos por una disminución a 11.6 ± 2.1 fmol/mg proteína y 231.6 ± 54.0 nmol/l en el grupo +125 d. Además, la progesterona se unió competitivamente a los GR placentarios; sin embargo, su unión disminuyó en el grupo 101-125 d. Los GR de los hígados materno y fetal presentaron un perfil inverso. Estos resultados permiten sugerir que las cabras cuando se encuentran en situaciones que amenazan su vida y la del feto tienen mecanismos innatos para abortar, salvando la vida de la madre y dando la oportunidad de una nueva gestación que permita la sobrevivencia de la especie.

Direct Corticosteroid Modulation of GABAergic Neurons in the Anterior Hypothalamic Area of GAD65-eGFP Mice

Corticosterone is known to modulate GABAergic synaptic transmission in the hypothalamic paraventricular nucleus. However, the underlying receptor mechanisms are largely unknown. In the anterior hypothalamic area (AHA), the sympathoinhibitory center that project GABAergic neurons onto the PVN, we examined the expression of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) of GABAergic neurons using intact GAD65-eGFP transgenic mice, and the effects of corticosterone on the burst firing using adrenalectomized transgenic mice. GR or MR immunoreactivity was detected from the subpopulations of GABAergic neurons in the AHA. The AHA GABAergic neurons expressed mRNA of GR (42%), MR (38%) or both (8%). In addition, in brain slices incubated with corticosterone together with RU486 (MR-dominant group), the proportion of neurons showing a burst firing pattern was significantly higher than those in the slices incubated with vehicle, corticosterone, or corticosterone with spironolactone (GR-dominant group; 64 vs. 11~14%, p<0.01 by chi2-test). Taken together, the results show that the corticosteroid receptors are expressed on the GABAergic neurons in the AHA, and can mediate the corticosteroid-induced plasticity in the firing pattern of these neurons. This study newly provides the experimental evidence for the direct glucocorticoid modulation of GABAergic neurons in the AHA in the vicinity of the PVN.

Expression of pituitary glucocorticoid receptor and 11β-hydroxysteroid dehydrogenase 1 in obese diabetic rats / 中华内分泌代谢杂志

Diabetic rat model was induced by high fat diet combined with streptozotocin (STZ). After the model was established, blood samples were taken from jugular veins to examine plasma adrenocorticotropic hormone (ACTH) and corticosterone, and hypothalamus and pituitary were removed for real-time PCR. There were no significant differences in basal plasma ACTH and corticosterone level among control, obese, and obese diabetic rats (P=0.07). The corticosterone rhythm in obese and obese diabetic rats was impaired. Hypothalamus glucocorticoid receptors (GR) mRNA expressions yielded similar results in the groups, but 11β-HSD1 mRNA expression in obese diabetic rats was up-regulated ( vs control rats, P<0.05 ). The expressions of GR and 11β-HSD1 in pituitary of obese diabetic and obese rats were significantly down-regulated (both P<0.05). In the obese diabetic rats, the impaired glucocorticoid negative feedback was partly due to down-regulation of 11 β-HSD1 and GR expressions in pituitary.

Simultaneous evaluation of in vivo glucocorticoid sensitivity and expression of glucocorticoid receptor alpha-isoform in rheumatoid arthritis patients / Avaliação concomitante da sensibilidade in vivo aos glicocorticóides e da expressão da isoforma alfa do receptor de glicocorticóide em pacientes com artrite reumatóide

OBJECTIVES: To analyze glucocorticoid (GC) sensitivity using intravenous very low dose dexamethasone suppression test (IV-VLD-DST) in patients with rheumatoid arthritis (RA) and its correlation with glucocorticoid receptor alpha-isoform (GRα) gene expression. METHODS: We evaluated 20 healthy controls and 32 RA patients with Health Assessment Questionnaire (HAQ) and Disease Activity Score 28 joints (DAS) scores and IV-VLD-DST and GRα expression in mononuclear cells. RESULTS: Basal cortisol and the percentage of cortisol reduction after IV-VLD-DST were lower in RA patients than in controls, whereas GRα expression was similar among groups. In the RA group there was an inverse correlation between GRα expression and the percentage of cortisol suppression that was not observed in controls. There was a direct relationship between DAS and GRα expression. CONCLUSIONS: Mechanisms involved in GC resistance observed in patients with RA are possibly not at the level of GRα gene expression, since it was similar among groups and GRα increased with disease activity.

OBJETIVOS: Determinar a sensibilidade aos glicocorticóides (GC) utilizando teste de supressão com dexametasona em doses muito baixas (IV-VLD-DST) em pacientes com artrite reumatóide (AR) e sua correlação com a expressão gênica da isoforma alfa do receptor glicocorticóide (GRα). MÉTODOS: Foram avaliados 20 controles saudáveis e 32 pacientes com AR com Health Assessment Questionnaire (HAQ) e Disease Activity Score 28 joints (DAS), IV-VLD-DST e expressão do GRα em células mononucleares. RESULTADOS: Cortisol basal e porcentagem de redução do cortisol após IV-VLD-DST foram menores no grupo AR do que nos controles, enquanto a expressão de GRα foi similar entre eles. No grupo com AR, ocorreu correlação negativa entre a expressão do GRα e a porcentagem de supressão do cortisol, enquanto nos controles não houve correlação. Ocorreu relação direta entre DAS e expressão de GRα . CONCLUSÕES: Sugerimos que os mecanismos envolvidos na resistência aos GC observada na AR não estejam ao nível da expressão gênica do GRα, já que esta é igual entre os grupos e aumenta com a gravidade da doença.

Changes of nuclear receptors-glucocorticoid receptors in locus ceruleus neurons of posttraumatic stress disorder-like rat / 解剖学报

Objective To investigate expression changes of nuclear receptors-glucocorticoid receptors (GR) in the locus ceruleus neurons of posttraumatic stress disorder(PTSD)like rats. Methods Sixty adult healthy male Wistar rats were enrolled in the experiment. PTSD-like rat model was established by single prolonged stress (SPS). There was no SPS stimulation in the control group and the rats of the other five groups were undisturbedly raised for 24 hours, 4 days,7 days,14 days and 28 days respectively after SPS stimulation.The expressions of glucocorticoid receptors in the locus ceruleus nucleus of all groups were detected with Nissl staining, immunohistochemistry,Western blotting and PCR, and image analysis and statistical analysis were performed. Results GR was distributed in the nucleus of coeruleus neurons, GR expression was showed after 24 hours, 4 days, 7 days treatment and gradually increased, restorative downregulation was seen after 14 days and 28 days, but still high(P<0.05). Conclusion After SPS, the GR locus ceruleus temporarily increased and then lowered, suggesting that PTSD rat locus coeruleus neurons in nuclear receptor-GR expression changes may directly involve in the continuing spirit of PTSD symptoms occurred in the development process.

Expression of glucocorticoid receptor mRNAs in glucocorticoid-resistant nasal polyps

Glucocorticoids (GCs) are the most effective group of medications available to treat inflammation. Although most patients with inflammation respond to GC, a small group of patients exhibit persistent GC-resistance with prolonged inflammation. Previously, it was proposed that the GC-resistance is caused by low amount of human GC receptor (hGR alpha) and/or excessive presence of a GC receptor isoform, hGR beta that was generated from alternative splicing of the hGR message. We have tested this hypothesis by investigating correlation between the expression pattern of hGR mRNAs in patients with inflammatory nasal polyps and the effectiveness of GC treatment.? We have performed reverse transcription PCR analysis of mRNAs coding each hGR alpha and hGR beta in nasal tissues.? hGR alpha mRNA was more expressed in patients with nasal polyps than in normal subjects. However, the elevated hGR alpha mRNA expression was decreased after GC treatment. Compared with hGR alpha mRNA expression, level of hGR beta mRNA expression was very low in all groups. In patients, hGR beta mRNA was expressed at a similar level regardless of GC efficacy, indicating that there is no correlation between the GC sensitivity and the expression level of hGR beta mRNA. Thus, persistent GC-resistance is not associated with low expression of hGRa or over- expression of hGR beta.

Expression of Glucocorticoid Receptor in Nasal Polyps and Nasal Mucosa / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Glucocorticoids are currently the most potent medication available for the treatment of nasal polyposis and allergic rhinitis, but exact mechanisms and cellular targets in the nasal mucosa are uncertain. Multifactorial effects of glucocorticoid are initiated by their binding to a specific cytoplasmic glucocorticoid receptor (GR). We performed this study to investigate the localization and distribution ot' human 4R and GR j3 isoform in nasal mucosa and to examine the influence of allergy and eosinophilic infiltration on GR and GR betaisoform expression in nasal polyps. MATERIALS AND METHODS: Nasal polyps (NP), middle turbinate mucosa (MT) and inferior turbinate (IT) mucosa were taken from 40 patients with chronic sinusitis and nasal polyps. We examined to have concomitant allergic rhinitis. Specimens were stained to quantify eosinophils and immunohistochemically stained to quantify GR and GR beta isaform in the unit area of tissues. RESULTS: Immunostaining of GR and GR betaisoform was predominantly localized in epithelial cell and infiltrating inflammatory cell in subepithelial layer, with lesser amounts in the endothelial cells and in the cells surrounding glands. Immunostaining of GR was mostly co-expressed with GR beta isoform. No correlation was found between Gk and GR beta isoform expression in subepithelial layer and the intensity of eosinophilic inflammation and allergy in NP. There was no significant differences in GR and GR beta isoform expression between NP, MT, and IT. CONCLUSION: Epithelial cells may be an important site of action for intranasal steroids, and the increased number of eosinophils infiltrating the mucosa and allergy did not amplify the number of immunostaining of GK and GR beta isoform.

Effects of NMDA receptor on glucocorticoid receptor mRNA levels in hippocampus of rats after scald burn stress / 第三军医大学学报

Objective To investigate the changes of glucocorticoid receptor (GR) gene expression in the hippocampus of rats following scald burn stress and the role of N methyl D aspartate (NMDA) receptor in this change. Methods Adult male Wistar rats inflicted with 30% TBSA full thickness scalding were applied as severe scalding stress model. GR mRNA levels in the hippocampus were detected with RT PCR. Results A significant decrease of GR mRNA levels was observed in the hippocampus 2 h after the scalding stress. The decrease could be inhibited when MK 801, an NMDA receptor antagonist, was administered prior to stress, and be augmented with the administration of NMDA, an NMDA receptor agonist, but not be affected by normal saline. Conclusion NMDA receptors are involved in the scalding stress induced down regulation of GR gene expression in the rat hippocampus.

THE EFFECTS OF CHRONIC ADMINISTRATION OF HYDROCORT- ISONE ON THE GLUCOCORTICOID RECEPTOR OF HEPATIC CYTSOL IN RATS / 第二军医大学学报

The daily intramuscular injections of hydrocortisone acetate for about 20 days (2 mg/100g body weight per day), resulted in a marked decrease of specific binding capacity (Ro) and an increase of the equilibrium dissociation constant (Kd) of the hepatic cytosol with [3H] dexamethasone in rats. There were no changes of Ro and Kd in the control groups after saline injection for about 20 days or a single injection of hydro-cortisone acetate 5 hours or 24 hours prior to sacrification of the animals. The results indicated the exsistence of down-regulation of glucocorticoid hormone to its homologous receptor after chronic admnistration of glucocrticoid hormone.