Lymphocyte Glucocorticoid Receptor Research Articles

Static electric field exposure decreases white blood cell count in peripheral blood through activating hypothalamic–pituitary–adrenal axis

ABSTRACT With the development of ultra-high-voltage (UHV) direct-current (DC) transmission, the health risk from the static electric field (SEF) generated by UHV DC transmission lines has drawn public attention. To investigate the effect of SEF exposure on white blood cell (WBC) count, mice were exposed to 56.3 kV/m SEF. Results revealed that total WBC count and lymphocyte count significantly decreased and serum levels of corticotropin-releasing hormone, adrenocorticotropic hormone and corticosterone (CORT) significantly increased after the exposure of 7d and 14d. All indices above recovered after the exposure of 21d. Analysis showed that the exposure of 7d and 14d could activate hypothalamic-pituitary-adrenal (HPA) axis. The increased CORT could bind to the glucocorticoid receptor (GR) in lymphocytes, and then promote the migration and apoptosis of lymphocytes. After the exposure of 21d, the magnitude of HPA axis activation declined through CORT-mediated negative feedback and the regulation of stress-related neural circuitry, so WBC count recovered.

BOS Is Associated With Increased Cytotoxic Proinflammatory CD8 T, NKT-Like, and NK Cells in the Small Airways.

Immunosuppression therapy after lung transplantation fails to prevent bronchiolitis obliterans syndrome (BOS) in many patients, primarily a disease of the small airways. We have reported that BOS is associated with a lack of suppression of cytotoxic mediators, and proinflammatory cytokines, in peripheral blood T, NKT-like (particularly CD8+) and NK cells. We also showed a loss of glucocorticoid receptor (GCR) in proinflammatory lymphocytes after transplant. It is unknown whether these proinflammatory lymphocytes target the small and/or large airways in BOS. Blood, bronchoalveolar lavage, large proximal, and small distal airway brushings were collected from patients with BOS (n = 10), stable lung transplant patients (n = 18), and healthy aged-matched controls (n = 10). Intracellular cytotoxic mediators (perforin/granzyme B), proinflammatory cytokines (IFNγ/TNFα), and expression of GCR were determined in lymphocytes subsets from cultured blood using flow cytometry. Increases in CD8 T cells, NKT-like cells, and NK cells were found in the small distal airways in BOS compared with stable patients and controls. An increase in perforin, granzyme B, IFNγ, TNFα, and a loss of GCR from these lymphocyte subsets was also found in BOS. GCR expression by CD8+ T cells from small airways correlated with FEV1 (R = 0.834, P = 0.039). Many of these changes significantly differed from those in the large airways. BOS is associated with increased cytotoxic/proinflammatory CD8+ T, NKT-like, and NK cells in the small airways. Treatments that increase GCR in these lymphocyte subsets may improve graft survival.

Effects of caloric restriction and low glycemic index diets associated with metformin on glucose metabolism and cortisol response in overweight/obese subjects: a case series study.

BackgroundTo determine whether cortisol secretion and glucocorticoid receptors in lymphocytes and monocytes are altered in patients with impaired glucose tolerance, and whether treatment with a hypocaloric diet and metformin could interfere with these aspects.MethodsThis is an analytical, interventional, case series study. Patients with impaired glucose tolerance were included. They received 500 mg of metformin twice daily and followed a low glycemic index diet for 16 weeks. Cortisol levels were assessed at 8:00 A.M. before and after use of 0.25 mg of dexamethasone at 11:00 P.M. the day before.ResultsSixteen subjects (9 men) were included. Normal basal levels of cortisol and adequate responses to the low dose of dexamethasone were observed before and after treatment. There was no significant correlation between the parameters evaluated and cortisol levels. Nevertheless, there was a strong correlation between the number of glucocorticoid receptors, BMI (r = 0.88; p = 0.02), and insulin AUC (r = 0.94; p = 0.005) before treatment; after treatment, all these associations ceased to exist.ConclusionThe cortisol secretion remained normal in the group of patients with impaired glucose tolerance. Treatment with metformin and diet did not change this condition. However, glucocorticoid receptor number had a strong correlation with insulin, due to insulin resistance, but this characteristic was lost after treatment.

Accumulation of cytoplasmic glucocorticoid receptor is related to elevation of FKBP5 in lymphocytes of depressed patients.

We have previously shown that patients with the major depressive disorder (MDD) exhibited elevated phosphorylation of the lymphocyte glucocorticoid receptor (GR) at serine 226 (S226). Here, we further analyse potential alterations of GR signalization in lymphocytes of MDD patients, i.e. the cytoplasmic/nuclear distribution of GR, levels of FK506-binding protein 5 (FKBP5) and glucocorticoid-induced leucine zipper (GILZ). The FKBP5 acts as an important regulator of GR activation, by decreasing ligand binding and impeding translocation of the receptor to the nucleus, while GILZ mediates glucocorticoid anti-inflammatory effects. Our result showed that the depressed patients had significantly higher GR levels in the cytoplasm compared to controls, which was accompanied by higher FKBP5 levels. Linear regression model demonstrated significantly higher correlation between FKBP5 and cytoplasmic GR than the presence of MDD itself or phosphorylation of nuclear GR at S226. There were no differences in the levels of GILZ isoforms. Therefore, the results suggest that accumulation of the GR in cytoplasm is related to the elevation of FKBP5, adding one more step in understanding altered GR signalling in lymphocytes, and potentially brain tissue, of MDD patients.

Lymphocyte glucocorticoid receptor expression level and hormone-binding properties differ between war trauma-exposed men with and without PTSD

Posttraumatic stress disorder (PTSD) has been shown to be associated with altered glucocorticoid receptor (GR) activity. We studied the expression and functional properties of the receptor in peripheral blood mononuclear cells (PBMCs) from non-traumatized healthy individuals (healthy controls; n=85), and war trauma-exposed individuals with current PTSD (n=113), with life-time PTSD (n=61) and without PTSD (trauma controls; n=88). The aim of the study was to distinguish the receptor alterations related to PTSD from those related to trauma itself or to resilience to PTSD. Functional status of the receptor was assessed by radioligand binding and lysozyme synthesis inhibition assays. The level of GR gene expression was measured by quantitative PCR and immunoblotting. Current PTSD patients had the lowest, while trauma controls had the highest number of glucocorticoid binding sites (Bmax) in PBMCs. Hormone-binding potential (Bmax/KD ratio) of the receptor was diminished in the current PTSD group in comparison to all other study groups. Correlation between Bmax and KD that normally exists in healthy individuals was decreased in the current PTSD group. Contrasting Bmax data, GR protein level was lower in trauma controls than in participants with current or life-time PTSD. Current PTSD is characterized by reduced lymphocyte GR hormone-binding potential and by disturbed compensation between Bmax and hormone-binding affinity. Resilience to PTSD is associated with enlarged fraction of the receptor molecules capable of hormone binding, within the total receptor molecule population in PBMCs.

Low expression of glucocorticoid receptors in children with steroid-resistant nephrotic syndrome

About 10-20 % of children with idiopathic nephrotic syndrome (NS) are steroid-resistant (SR). Low expression of glucocorticoid receptors (GRs) has been associated with poor response to steroids in a variety of autoimmune diseases. This study was done to assess the expression of cytoplasmic GRs for CD3 and CD14 in children with NS. Expression of cytoplasmic GRs in lymphocytes (CD3(+)/GR) and monocytes (CD14(+)/GR) in the peripheral blood were assessed in 51 children with NS before the start of therapy by flow cytometry. Patients were divided into two groups: 30 children who were steroid-sensitive (SSNS) and 21 children who had initial steroid resistance (SRNS). Twenty age- and sex-matched healthy children served as controls. Expression of CD3(+)/GR was significantly lower in SRNS in comparison to SSNS patients and controls (p < 0.0001). Similarly, expression of CD14(+)/GR was significantly lower in SRNS in comparison to SSNS patients (p < 0.0001) and controls (p = 0.002). CD3(+)/GR and CD14(+)/GR expression were not significantly different in SSNS patients compared with controls (p = 0.06 and 0.07 respectively). Patients with initial SRNS showed decreased GR expression in peripheral blood mononuclear cells (PBMC) before starting therapy, and this low expression may be one of the pathophysiological mechanisms of steroid resistance in these children.

How Does Lymphocyte Glucocorticoid Receptor Expression and Salivary Cortisol Relate to Trauma Exposure and Posttraumatic Stress Disorder?

How Does Lymphocyte Glucocorticoid Receptor Expression and Salivary Cortisol Relate to Trauma Exposure and Posttraumatic Stress Disorder? Hypothalamus-pituitary-adrenal axis functioning and glucocorticoid receptor number on lymphocyte subsets were investigated in patients with posttraumatic stress disorder related to type I trauma, trauma-exposed subjects without posttraumatic stress disorder and trauma-unexposed control subjects (n=13 per group) applying a detailed endocrinological assessment. Salivary cortisol profiles were obtained, first, as diurnal baseline cortisol (unstimulated), and second, after dexamethasone administration (stimulated cortisol) to investigate the negative feedback inhibition of the hypothalamus-pituitary-adrenal axis. For further assessment of glucocorticoid receptor binding, glucocorticoid receptor counts on lymphocytes were obtained from blood samples.

Effects of housing and short-term transportation on hormone and lymphocyte receptor concentrations in beef cattle

The experiment was designed to evaluate the effects of housing system and short-term transportation on the pituitary and adrenal response and on blood progesterone concentrations of beef cattle. Since the use of steroid hormones in farm animals has been banned in the EU (Council Directive 96/22/EC), it seems important to study the possible modifications in serum progesterone concentrations induced by stress in cattle. Thirty-two, 6 months old male Piedmontese beef cattle (16 reared in a littered loose house, Group A, and 16 housed in a littered tying stall barn, Group B) were blood sampled at T1 (6 months old), T2 (12 months old), T3 (18 months old, before transportation to the slaughterhouse) and T4 (after transportation to the slaughterhouse) in order to measure hormonal concentrations and lymphocyte glucocorticoid (GR) and β-adrenergic (β-AR) receptor concentrations. Circulating hormone concentrations were measured using commercial radioimmunoassay kits, whereas lymphocyte receptor density was determined through binding assays. In beef cattle housed in tie stall barn a significant increase in serum cortisol concentration was observed at T3, whereas there was no effect of the housing system on blood progesterone concentrations. Short-term transportation caused a significant increase in blood cortisol and catecholamine concentrations in both groups, whereas lymphocyte GR and β-AR significantly decreased in Group A. Our data confirm the activation of the hypothalamic–pituitary–adrenal axis and the catecholaminergic system in short-term transportation and suggest that the stress-induced increase in circulating progesterone concentrations does not exceed the limit established by pending legislation.

The Effect of Restraint Stress on Glucocorticoid Receptors in Mouse Spleen Lymphocytes: Involvement of the Sympathetic Nervous System

Objective: Reciprocal pathways of interaction between the nervous and immune systems during stress may be regulated by stress-induced circulating glucocorticoids that act via type II glucocorticoid receptors (GRs). The aim of the present study was to investigate the effect of restraint stress on GRs in lymphocytes and the role of the sympathetic system in this effect. Methods: We used male Balb/c mice which were adrenalectomized 3 days before exposure to restraint stress (4 h). Specific binding of ³H-dexamethasone (Dex) and the expression of GR protein were measured in the cytosol of spleen cells. Results: Restraint stress caused a significant increase in the maximal binding of ³H-Dex to GRs in the cytosol of spleen cells but not in the binding affinity. In correlation with this increase in binding, restraint stress caused an increase in the amount of GR protein. To establish the relation of the nervous system in this stress response, we blocked the autonomic innervations to the spleen with the ganglionic blocker chlorisondamine. This blocker abrogated the stress-induced increase in the binding of ³H-Dex to GRs and in the GR protein levels. Abrogation of the stress response was also achieved by blocking β-adrenergic receptors. Conclusion: These results suggest that stress-induced increase in the level of GRs is mediated by the sympathetic nervous system via β-adrenergic receptors. It is possible that stress modulation of lymphocyte GR levels may be implicated in the bidirectional communication between the nervous and the immune systems.

Natural killer cell cytotoxicity and lymphocyte perforin expression in veterans with posttraumatic stress disorder

Objective To examine the effect of posttraumatic stress disorder (PTSD) on the measures of immune function and the hypothalamic–pituitary–adrenal axis components, and to determine whether additional life stressors affect measured variables. Methods We simultaneously examined the natural killer cell cytotoxicity (NKCC), perforin and glucocorticoid receptor (GCR) expression in natural killer (NK) and cytotoxic T (CD8) cells, as well as serum cortisol concentration in a group of Croatian war veterans with chronic, combat-related PTSD ( n = 29) and a group of healthy, age-matched men ( n = 13). PTSD patients were divided into two subgroups: compensation-seeking ( n = 15) and retired or compensation non-seeking ( n = 14) subjects. The former includes those involved in the process of getting disability-based army retirement as an additional life stressor. Results NKCC was decreased in both PTSD groups when compared to controls. Impairment of NKCC could not be attributed to the perforin expression as perforin was not decreased in comparison to controls. Moreover, the increased level of perforin was recorded in NK cells of retired PTSD subjects. Both PTSD groups shared an increased relative quantity of GCR in lymphocytes, whereas no difference between the groups in the baseline levels of serum cortisol was observed. Conclusions Diminished NKCC was not accompanied by perforin insufficiency in PTSD subjects, and other causes should be examined. An additional life stressor does not contribute considerably to either immune or endocrine system related changes.

Lymphocyte glucocorticoid receptor resistance and depressive symptoms severity: A preliminary report

Objective Assessment of the temporal interrelationship of neuropsychiatric parameters requires technologies allowing frequent biological measurements. We propose glucocorticoid receptor (GR) function of lymphocytes to assess the temporal relationship between glucocorticoid resistance and the course of major depressive disorder. Method Dexamethasone suppression of lymphocyte proliferation was in vitro assessed via 5-bromo-2′ deoxyuridine (BrdU) incorporation in DNA. Optimal conditions were determined using blood of healthy volunteers. Thereafter the relation between depression severity (Hamilton Depression Rating Scale, HDRS, scores), lymphocyte proliferation and morning cortisol levels in blood was studied in thirteen depressed patients, mostly with a history of treatment resistance. Results Recovery from depression was not directly associated with changes in lymphocyte glucocorticoid resistance. However, a negative correlation was observed between HDRS and BrdU incorporation and a positive correlation between morning cortisol and BrdU incorporation. No significant correlation was found between cortisol and HDRS. Regression analyses showed that HDRS was related to both suppression of BrdU incorporation ( β − 0.508, p < 0.001) and cortisol levels ( β 0.364, p = 0.001) in a highly significant model ( F 2,60 = 14,244, p < 0.001) Except for one case, such relation could not be found within patients. Conclusion Our preliminary results suggest a mutual relation between lymphocyte GR function, morning cortisol levels and MDD symptom severity. A direct relation between glucocorticoids resistance and recovery may not exist, but glucocorticoid resistance might attenuate or prevent recovery. It is clear that additional studies using larger and more homogenous groups of MDD patients are required to support our findings.

Enhanced cortisol suppression to dexamethasone associated with Gulf War deployment

To examine whether PTSD or post-deployment health symptoms in veterans of the first Gulf War (Operation Desert Shield/Storm) are associated with enhanced suppression of the pituitary-adrenal axis to low-dose dexamethasone (DEX). Plasma cortisol and lymphocyte glucocorticoid receptor (GR) number were measured at 08:00 h on two consecutive days, before and after administration of 0.5mg of DEX at 23:00 h in 42 male Gulf War veterans (14 without psychiatric illness, 16 with PTSD only, and 12 with both PTSD and MDD) and 12 healthy male veterans not deployed to the Gulf War or another war zone. In the absence of group differences in basal cortisol levels or GR number, Gulf War veterans without psychiatric illness and Gulf War veterans with PTSD only had significantly greater cortisol suppression to DEX than non-deployed veterans and Gulf War veterans with both PTSD and MDD. Gulf War deployment was associated with significantly greater cortisol suppression to DEX controlling for weight, smoking status, PTSD, and MDD; PTSD was not associated with response to DEX. Among Gulf War veterans musculoskeletal symptoms were significantly associated with cortisol suppression and those who reported taking anti-nerve gas pills (i.e., pyridostigmine bromide) during the war had significantly greater DEX-induced cortisol suppression than those who did not. The data demonstrate that alterations in neuroendocrine function are associated with deployment to the Gulf War and post-deployment musculoskeletal symptoms, but not PTSD. Additional studies are needed to examine the relationship of enhanced glucocorticoid responsivity to deployment exposures and chronic unexplained medical symptoms in Gulf War veterans.

Cognitive Effects of Intravenous Hydrocortisone in Subjects with PTSD and Healthy Control Subjects

On the basis of peripheral (nonbrain) neuroendocrine findings in subjects with posttraumatic stress disorder (PTSD), it has been hypothesized that these individuals also have a greater central (brain) sensitivity to glucocorticoids. In nonpsychiatric subjects, it has been found that working and declarative memory performance is selectively impaired by acute glucocorticoid administration. We hypothesized that subjects with PTSD, as compared to nonpsychiatric controls, would show greater impairments in verbal declarative memory and working memory, but not attention, following exogenous glucocorticoid administration. These data are part of a larger study using functional neuroimaging and peripheral HPA axis measures in these same subjects. Subjects underwent a 0.5-mg dexamethasone suppression test and measurement of basal cortisol, basal plasma lymphocyte glucocorticoid receptor number, and postdexamethasone cortisol on a separate day. Under double-blind randomized crossover conditions, 17-mg hydrocortisone or placebo was administered by intravenous (i.v.) bolus to 15 medication-free PTSD subjects (4 female) and 12 nonpsychiatric control subjects (4 female) matched by age, sex, and education level. Participants then underwent positron emission tomography (PET) scanning and 90 min after the initial drug/placebo administration, cognitive testing was then performed. By repeated measures ANCOVA (covaried for baseline performance on that neuropsychological test), neither attention tasks of digit span forward nor backward showed significant change. However, there were significant drug (F = 17.644, df = 1,25 P < 0.001), group (F = 4.383, df = 1,25 P = 0.048), and drug by group interactions (F = 4.756, df = 1,25 P = 0.040) for verbal declarative memory. By t-test, there was not a difference in baseline performance on this measure between subject groups. The subject group with PTSD experienced a greater decline in verbal declarative memory performance following hydrocortisone administration. For working memory, there were significant group (F = 6.048, df = 1,25 P = 0.022) and drug by group interactions (F = 6.048, df = 1,25 P = 0.022) for verbal declarative memory. By t-test, there was not a difference in baseline performance on this measure between subject groups. The hydrocortisone administration led to impairment in working memory in the group of subjects with PTSD, but not in the control subject group. Exploratory correlations between percent cortisol suppression following dexamethasone and baseline plasma lymphocyte glucocorticoid receptor number with declarative and working memory measures among subject groups separately and in a combined way revealed a negative correlation between lymphocyte glucocorticoid receptor density and working memory (r = -0.54, df = 25, P = 0.008). Brain sensitivity to glucocorticoids appears to be greater in subjects with PTSD. Heightened vulnerability of declarative memory in subjects with PTSD may indicate hippocampal involvement, whereas working memory vulnerability suggests additional brain regions (prefrontal, cingulate, temporal, and parietal cortices) and neurotransmitter systems (dopamine and serotonin) particularly sensitive to glucocorticoids in persons with PTSD.

Expression of human glucocorticoid receptor in lymphocytes of patients with autoimmune hepatitis.

Background and aim: Alternative splicing of human glucocorticoid receptor (hGR) premessenger RNA (mRNA) generates two highly homogenous isoforms, termed hGRalpha and hGRbeta. hGRalpha is a ligand-activated transcription factor, which, in the hormone-bound state, modulates the expression of glucocorticoid-responsive genes by binding to specific glucocorticoid response element DNA sequences. In contrast, hGRbeta may be an endogenous inhibitor of glucocorticoid action and transcriptionally inactive. hGRbeta protein has been known to correlate with the development of glucocorticoid resistance. Glucocorticoids can effectively relieve autoimmune hepatitis (AIH), but some patients with this disease are refractory even when glucocorticoids are administered. The aim of this study was to determine the incidence of hGRbeta mRNA in patients with AIH by reverse transcription polymerase chain reaction (RT-PCR), and to compare the clinical characteristics of hGRbeta-positive and -negative patients with AIH. Materials and methods: RNA was obtained from peripheral blood mononuclear cells (PBMCs) of 62 patients, consisting of 26 with AIH, 10 with primary biliary cirrhosis (PBC), seven with chronic viral hepatitis (CVH), 10 with ulcerative colitis (UC), six with pemphigus, and three with systemic lupus erythematosus (SLE), and 10 healthy volunteers. The total RNA obtained was reverse transcribed, the resulting complementary DNA amplified using specific primers for hGRalpha and hGRbeta. Results: The hGRalpha mRNA was detected in RNA from PBMCs of all patients and healthy volunteers. The hGRbeta mRNA was detected in 15 (57.6%) patients with AIH. This incidence was significantly higher than that for patients with PBC (0%) or CVH (28.6%) or for healthy volunteers (20.0%) ( [Formula: see text] ). Of the hGRbeta-positive and -negative groups, serum ALT and total bilirubin (TB) levels were significantly higher in the positive group ( [Formula: see text] ). The total dose of glucocorticoid was higher in the positive group, but the difference was not statistically significant. However, the average monthly dose was significantly higher in the positive group ( [Formula: see text] ). The rate of relapse of AIH was significantly higher in the positive group (60.0%) than in the negative (10.0%) ( [Formula: see text] ). The rate of usage of immunosuppressive drugs was higher in the positive group (33.3%) than in the negative (18.2%), but the difference was not statistically significant. Conclusions: These data show that hGRbeta expression in PBMCs of patients with AIH assessed by RT-PCR is closely associated with resistance to glucocorticoids which affects the outcome of therapy with this drug.

Road transportation affects blood hormone levels and lymphocyte glucocorticoid and β-adrenergic receptor concentrations in calves

The effect of transportation on blood cortisol and catecholamine levels, lymphocyte glucocorticoid receptor (GR) and β-adrenergic receptor (β-AR) concentrations was investigated in calves. Blood samples were collected from 24 six-month-old calves before departure ( T 0), on arrival ( T 1), and at 24 h ( T 2) and one week ( T 3) after arrival. Animals were loaded and transported about 950 km, from the Midy-Pyrénes region (Cahors, France) to the Piedmont region (Italy), over a total of 14 h. Serum cortisol levels and plasma catecholamines (adrenaline, noradrenaline) were determined by radioimmunoassay. Lymphocyte GRs and β-ARs were measured through binding assays. A significant ( P<0.05) increase in cortisol and catecholamine concentrations was observed immediately after transport. The increase in hormone levels at time T 1 was negatively correlated with lymphocyte GR and β-AR concentrations. At times T 2 and T 3, blood cortisol and catecholamine levels and lymphocyte GRs and β-ARs returned to normal. The results demonstrate the activation of the hypothalamic-pituitary-adrenal axis and the catecholaminergic system in long-term transported calves. However, these systems returned to normal within 24 h after the end of transport.

Expression of glucocorticoid receptors in mononuclear cells in nephrotic syndrome.

Coulter flow cytometry was used to determine glucocorticoid receptors (GCR) in the peripheral blood cells of patients with nephrotic syndrome. The expression of GCR in the lymphocytes (CD3/GCR) and monocytes (CD14/GCR) of peripheral blood of 23 (age 4.9+/-2.7 years) children with steroid-sensitive nephrotic syndrome was assessed before treatment (proteinuria >50 mg/kg per 24 h), after 4-6 weeks of prednisone treatment, without proteinuria, and in remission, without proteinuria and without any treatment. Before treatment the expression of CD3/GCR was 61.8+/-18.3% and CD14/GCR 43.6.8+/-20.3%; this did not differ from the results of the normal control group ( P>0.05). However, after treatment GCR expression in lymphocytes was 50% ( P<0.001) and in monocytes about 20% lower ( P<0.05). In remission, the GCR expression increased and did not differ from the results before treatment ( P>0.05). A positive correlation between the serum cortisol concentration and the expression of CD3/GCR was found ( r=0.504, P=0.02). In summary, we report that in children with steroid-sensitive nephrotic syndrome, prednisone treatment causes the temporary decrease of the expression of GCR in lymphocytes. A positive correlation between GCR expression and serum cortisol was found. A decrease in GCR expression in monocytes did not correlate with cortisol concentration.

Expression of human glucocorticoid receptor in lymphocytes of patients with autoimmune hepatitis

Expression of human glucocorticoid receptor in lymphocytes of patients with autoimmune hepatitis

IL-18 induces beta isoform of human glucocorticoid receptor in lymphocytes, to lead the glucocorticoid unresponsiveness in ulcerative colitis

IL-18 induces beta isoform of human glucocorticoid receptor in lymphocytes, to lead the glucocorticoid unresponsiveness in ulcerative colitis

The cortisol and glucocorticoid receptor response to low dose dexamethasone administration in aging combat veterans and holocaust survivors with and without posttraumatic stress disorder

Background: Because alterations in cortisol negative feedback inhibition associated with aging are generally opposite of those observed in posttraumatic stress disorder (PTSD), we examined the cortisol and glucocorticoid receptor (GR) response to dexamethasone (DEX) in older trauma survivors. Methods: Twenty-three Holocaust survivors (9 men, 14 women), 27 combat veterans (all male), and 10 comparison subjects (7 men, 3 women) provided samples for plasma or salivary cortisol and glucocorticoid receptor determination in mononuclear leukocytes at 8:00 am on the day of, and following, 0.5 mg of DEX at 11:00 pm. Results: Greater percent suppression of cortisol and lymphocyte GR was observed in older trauma survivors with PTSD compared to survivors without PTSD and comparison subjects. There was a significant main effect of depression in the direction of reduced suppression following DEX, consistent with the effects of DEX in major depressive disorder patients. Responses to DEX were uncorrelated with PTSD symptom severity, but cortisol suppression was associated with years elapsed since the most recent, but not focal, traumatic event. Conclusions: The response to DEX is generally similar in older and younger trauma survivors, but the findings suggest that age, symptom severity, and lifetime trauma exposure characteristics may influence this response.

Involvement of the glucocorticoid receptor in the pathogenesis of rheumatoid arthritis.

The glucocorticoid receptor (GR) is a ligand-inducible transcription factor which controls the expression of several genes. Its cognate ligand, the glucocorticoids, induces receptor activation by binding to the cytoplasmic located receptor, ultimately leading to translocation of the receptor/hormone complex into the nucleus and the regulation of gene activity. Because glucocorticoids are widely used for suppression of inflammation in rheumatoid arthritis (RA), we investigated whether the expression level of GR is correlated with RA. We designed a study to detect the total amount of GR in lymphocytes of untreated RA patients, glucocorticoid-treated RA patients, and healthy controls. We observed a significant change in the expression levels of GR. Untreated RA patients exhibited a significantly higher amount of GR than the healthy controls, whereas glucocorticoid-treated RA patients showed a strongly decreased receptor density. These results seem to reflect a functional dysregulation of the HPA axis and may lead to a better understanding of the pathogenesis of RA.