Coronary Disease ; drug therapy ; metabolism ; Female ; Humans ; Male ; Receptors, Glucocorticoid ; metabolism

OBJECTIVETo detect the expression of glucocorticoid receptor (GR) alpha and beta in nasal polyps, and analyze the possible relationship between over-expression of GR beta and steroid insensitivity.

METHODSThe expression of GR alpha and GR beta was examined by immunohistochemical SP method in the specimens from 17 patients with recurring nasal polyp, 18 patients with chronic rhinosinusitis and nasal polyp (CRSwNP), and 12 patients with chronic rhinosinusitis without nasal polyp (CRSsNP) that did not recur during follow-up for 1.5 - 2 years.

RESULTSThe difference of numbers of GR alpha-positive cells (x +/- s) between groups with recurrent nasal polyp (20.2 +/- 6.9), CRSwNP (20.7 +/-7.2) , CRSsNP (16.9 +/- 7.2) and normal subjects (16.1 +/- 5.3) was not significant (P > 0.05). The numbers of GR beta-positive cells in recurring group (34.2 +/- 7.4) or CRSwNP (31.5 +/- 5.9) were higher than that in CRSsNP (19.8 +/- 7.8) and normal group (10.1 +/- 6.7) respectively (all P < 0.05). There was a trend toward higher level in recurring polyp compared with that of CRSwNP patients without recurrence in follow-up period, although this was not statistically different (P = 0.558). The difference of GR beta/GR alpha ratios (x +/- s) in recurring specimens (1.80 +/- 0.47) and CRSwNP group (1.65 +/- 0.49) was significant compared with normal group (0.77 +/- 0.66) respectively (P < 0.05), while there was no significance compared with CRSsNP (1.23 +/- 0.27, P > 0.05).

CONCLUSIONSThe high expression of GR beta in nasal polyp is related to the development of nasal polyp.

Adult ; Aged ; Chronic Disease ; Female ; Humans ; Male ; Middle Aged ; Nasal Polyps ; metabolism ; Receptors, Glucocorticoid ; metabolism ; Rhinitis ; metabolism ; Sinusitis ; metabolism

OBJECTIVEThe expression of glucocorticoid receptor (GR) expression in obstructive sleep apnea hypopnea syndrome (OSAHS) in children is currently unknown. The aim of this study was to determine the GR-alpha and GR-beta status in the adenoidal tissues in children with OSAHS.

METHODSThirty-four pediatric patients (aged 3-14 years, median 7.8 years) had sleep study with polysomnography before adenoidectomy. According to the criteria of apnea hypopnea index (AHI) > or = 5 /h or/and apnea index (AI) > or = 1/h, they were divided into OSAHS and non-OSAHS sub groups. The study was based on fluorescent quantitative PCR (FQ-RT-PCR) for the mRNA expression of GR-alpha and GR-beta in the adenoidal tissues in children.

RESULTSGR isoforms mRNA encoding for expression of both GR-alpha and GR-beta were detected in the adenoids of all children. GR-alpha mRNA level [(9.40 +/- 3.06) x 10(5) cDNA copies/microg total RNA] in the adenoidal tissues in OSAHS was lower than those in the non-OSAHS [(1.60 +/- 0.26) x 10(6) cDNA copies/microg total RNA] (F = 40.285, P < 0.001), whereas no differences found for GR-beta [(1.57 +/- 0.35) x 10(4) cDNA copies/microg total RNA, (1.52 +/- 0.18) x 10(4) cDNA copies/microg total RNA]. GR-alpha/GR-beta ratio was 62.3 +/- 20. 3 in OSAHS and 107.4 +/- 24.4 in non-OSAHS. AHI or AI was not related to the mRNA levels of GR-alpha and GR-beta in OSAHS or non-OSAHS.

CONCLUSIONSGR-alpha and GR-beta were detectable in the adenoidal tissues in children. These data indicated that the relationship between the expressions of GR and the clinical significance in OSAHS need further and profound investigation.

Adenoids ; metabolism ; Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; RNA, Messenger ; genetics ; Receptors, Glucocorticoid ; metabolism ; Sleep Apnea, Obstructive ; metabolism

OBJECTIVETo explore the expressions of glucocorticoid receptor (GCR) and nuclear factor-kappaB (NF-kappaB) in patients with stable chronic obstructive pulmonary disease (COPD).

METHODSBronchial biopsies and blood specimens were obtained from 8 smokers with stable COPD (COPD group) and 8 nonsmokers with normal lung function (control group). The expressions of NF-kappaB and GCR in nucleus protein of bronchial biopsies and peripheral blood lymphocyte from these two groups were examined by Western blot.

RESULTSThe expressions of GCR in nuclear protein of peripheral blood lymphocyte and the bronchial biopsies, especially in bronchi, were significantly lower in COPD group than in control group (P<0.05, P <0.01). Also, the expressions of NF-kappaB in nuclear proteins of the bronchial biopsies and peripheral blood lymphocyte were significantly higher in COPD group than in control group (P<0.05). The expressions of NF-kappaB and GCR were significantly higher in bronchial biopsies than in peripheral blood lymphocyte in both groups (P<0.05, P<0.01).

CONCLUSIONChronic inflammation, especially airway inflammation, still exists in patients with stable COPD, as suggested by the different expressions of GCR and NF-kappaB between COPD patients and normal controls.

Aged ; Female ; Humans ; Male ; Middle Aged ; NF-kappa B ; metabolism ; Pulmonary Disease, Chronic Obstructive ; metabolism ; Receptors, Glucocorticoid ; metabolism

OBJECTIVETo explore the role and mechanism of glucocorticoid (GC) in the harmful bio-effects of electromagnetic irradiation.

METHODSRats were exposed to 65 mW/cm(2) electromagnetic wave for 20 min. At 10 min, 30 min, 3 h, 12 h after irradiation, their learning and memory abilities were tested by Morris water maze. The levels of corticosterone (CORT) in serum were measured by radioimmunoprecipitation assay and the changes of total glucocorticoid receptor (GR) expression and GR nuclear translocation in rat hippocampus were measured by reverse transcription-polymerase chain reaction and Western blot.

RESULTSThe rats had learning and memory deficits at 10 min, 30 min and 3 h after irradiation, but at 12 h had no difference from the normal control. The levels of corticosterone in serum increased significantly at 10 min, 30 min, decreased at 3 h and increased significantly compared with 12 h after irradiation. GR mRNA and total GR protein expression in rat hippocampus had no significant changes at 10 min, 30 min after irradiation. At 3 h, 12 h GR mRNA expression significantly decreased by 69%, 76% respectively and GR total protein decreased by 58%, 67% respectively. There were significant differences between the two groups and the corresponding controls (P<0.05). And compared with the control, the GR nuclear translocation increased significantly at 3 h and 12 h (P<0.05).

CONCLUSIONGC may take part in the injury to learning and memory abilities after electromagnetic irradiation, and the non-genomic and genomic effects of GC may play a major role in the early and late stage, respectively.

Animals ; Corticosterone ; blood ; Electromagnetic Fields ; adverse effects ; Glucocorticoids ; blood ; Hippocampus ; metabolism ; radiation effects ; Male ; Rats ; Rats, Wistar ; Receptors, Glucocorticoid ; metabolism

AIMTo investigate the changes of glucocorticoid receptor (GR) in rat brain regions with chronic immobilization stress and the influence of Chinese herbs.

METHODSWe copied the rat model of chronic immobilization stress (180 min daily, repeated 7 days or 21 days), and characterized the changes of GR in hippocampus CA1, cortex, dentate gyrus via immunohistochemistry integrated image analysis.

RESULTSThe contents of glucocorticoid receptors in hippocampus CA1 , cortex, dentate gyrus were increased and the intensity of immunity reaction was significantly stronger in the model group of 7 days than that in the normal control group (P < 0.05). The contents of GR were significantly decreased and the intensity of immunity reaction was weaken in the model group of 21 days (P < 0.05).

CONCLUSIONCompared with the model group of 21 days, the contents of GR were significantly increased and immunity reaction was intensified in three groups of treatment with Chinese herbs (P < 0.05), in which the group treated with soothing-liver herbs Xiaoyaopowder was the best.

Animals ; Brain ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Glucocorticoid ; drug effects ; metabolism ; Restraint, Physical ; Stress, Physiological

OBJECTIVE: To construct mesangial cell lines over- or under- expressing glucocorticoid receptor beta (GRbeta), to investigate the effect of GRbeta on glucocorticoid biological function, and to determine whether the overexpression of GRbeta explains the glucocorticoid-resistant in glomerular mesangial cells (GMCs). METHODS: The recombinant human sense or anti-sense gene of GRbeta was transferred into the rat GMCs by retrovirus-mediated stable transfection technique. Expression of hGRbeta mRNA in GMCs was determined by reverse transcription of total RNA followed by quantitative reverse transcription-polymerase chain reaction (RT-PCR), and the product of RT-PCR was then analyzed by gene sequencing. The expression of hGRbeta protein in GMCs was tested by Western blot. The inhibitory rate of dexamethasone-mediated cells on lipopolysaccharide (LPS)-stimulated GMC proliferation was detected to assess the effect of GRbeta at different expression levels on the glucocorticoid action. The cell proliferative activity in different cells with different levels of GRbeta was tested by MTT chromatometry. The change of cell cycle was analyzed by flow cytometry. RESULTS: RT-PCR and gene sequencing showed that the recombinant sense and anti-sense genes were correctly integrated into genomic DNA of mesangial cells. The protein expression tested by Western blot showed that GRbeta in cells inserted with the sense hGRbeta gene was higher than those cells inserted with the anti-sense hGRbeta gene (109.74+/-10.63 vs. 19.08+/-1.01, P<0.05). The inhibitory rate of cell proliferation induced by dexamethasone was lower in GMCs transfected with sense hGRbeta gene than those transfected with anti-sense hGRbeta gene (18.47%+/-2.12% vs. 60.33%+/- 5.29%,P<0.05). Under the inhibition of dexamethasone, the decreased cell number of S-stage cells was significantly lower, and the increased cell number of G1- stage cells was significantly higher in GMCs transfected with sense hGRbeta gene than those of non-transfected cells. CONCLUSION The overexpression of GRbeta may inhibit the glucocorticoid action in GMCs. The GRbeta level in mesangial cells may be an important factor in determining whether they are sensitive or resistant to glucocorticoid.
Animals ; Cell Line ; Dexamethasone ; pharmacology ; Glucocorticoids ; pharmacology ; Male ; Mesangial Cells ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Glucocorticoid ; genetics ; metabolism ; Transfection

Human monocyte leukemia cell line THP-1 was stimulated with lipopolysaccharide (LPS) to simulate the sepsis model and the expression of human glucocorticoid receptor-alpha (GR-alpha) mRNA in montocytes with endotoxin tolerance was investigated. THP-1 cells were cultured in serum-free medium, randomly divided into groups A, B, C, D and E, and stimulated with 0, 10, 10, 100, 0 ng/mL LPS for 24 h followed with 100, 100, 10, 100, 0 ng/mL LPS for another 24 h respectively. The expression of GR-alpha mRNA was detected by semi-quantitative reverse transcriptional polymerase chain reaction. Tumor necrosis factor-alpha (TNF-alpha) was determined by enzyme linked immunosorbent assay (ELISA). The results showed that the A values of GR-alpha/beta-actin in groups A, B, C, D and E was 0.607 +/- 0.006, 0.368 +/- 0.005, 0.484 +/- 0.008, 0.509 +/- 0.004 and 0.564 +/- 0.014 respectively with the difference being significant among the groups (P < 0.05). The GR-alpha mRNA expression was negatively correlated with the TNF-alpha expression (P < 0.01). It was concluded that the down-regulation of the expression of GR-alpha mRNA in endotoxin tolerance THP-1 cells might play an important role in the development of endotoxin tolerance in THP-1 cells.
Drug Tolerance ; Endotoxins/*pharmacology ; Leukemia, Monocytic, Acute/*metabolism ; Leukemia, Monocytic, Acute/pathology ; Monocytes/*metabolism ; RNA, Messenger/biosynthesis ; RNA, Messenger/genetics ; Receptors, Glucocorticoid/*biosynthesis ; Receptors, Glucocorticoid/genetics ; Tumor Cells, Cultured

Animals ; Brain ; growth & development ; metabolism ; Emotions ; Glucocorticoids ; therapeutic use ; Humans ; Memory ; RNA, Messenger ; analysis ; Receptors, Glucocorticoid ; analysis ; genetics ; physiology

OBJECTIVETo investigate the effects of glucocorticoid receptor antagonist-M8046 on the behavior and the cyclooxygenase-2/prostaglandin E2( COX-2/PGE2) expression in spinal cord dorsal horn and dorsal root ganglia (DRG) in chronic constrictive injury (CCI) rats.

METHODSOne hundred and forty-four male SD rats were randomly divided into 4 groups, 36 rats in each group: Sham operation group (Sham), chronic constrictive group (CCI), M8046 treated group (M8046) and solvent controlled group (Sc). M8046 3 mg/(kg x d) intraperitoneal injection was given after operation in group M8046. Paw thennal withdrawal (PTWL) and paw mechanical withdrawal threshold (PMWT) of rats were measured on 2 pre-operative and 1, 3, 7, 10, 14 post-operative days. The spinal cord and L15 DRG of the operated side was removed at 3, 7, 14 days after surgery. The change of COX-2 and PGE2 expression was determined by immunohistochemical staining and ELISA separately.

RESULTSPTWL and PMWT in CCI group were significantly lower than those in Sham group on every post-operative day (P < 0.05). PTWL and PMWT in M8046 group were significantly higher than those in CCI group on 7, 10, 14 post-operative day (P < 0.05). In spinal dorsal horn, the level of COX-2 and PGE2 expression in CCI group was significantly higher than that in Sham group (P < 0.05). M8046 could significantly attenuate the activation of COX-2 and PGE2 induced by CCI (P < 0.05). The expression of COX-2 and PGE2 in DRG was similar to that in spinal dorsal horn.

CONCLUSIONThe effects of M8046 ameliorate the CCI-induced neuropathic pain may be related to attenuate the expression of COX-2 and PGE2 in spinal cord and DRG.

Animals ; Cyclooxygenase 2 ; metabolism ; Dinoprostone ; metabolism ; Ganglia, Spinal ; drug effects ; metabolism ; Male ; Neuralgia ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Glucocorticoid ; antagonists & inhibitors ; Spinal Cord ; drug effects ; metabolism