Chronic Glucocorticoid Treatment Research Articles

A High Fat diet containing Fish oil reduces weight gain and metabolic syndrome associated with glucocorticoid therapy

Obesity and metabolic syndrome are now recognized as significant health concerns for survivors of pediatric Acute Lymphoblastic Leukemia (ALL) and are consequences of their treatment. The majority of weight gain occurs during the induction phase of therapy (first 28 days), when patients receive various chemotherapies in addition to high dose glucocorticoids. Physiological levels of glucocorticoids are required for metabolic control, but chronic exposure to elevated doses has been linked to metabolic disease including type 2 diabetes and obesity. Nutrition plays an important role in the development of obesity and is also amongst the few adjustable parameters in the treatment of pediatric ALL. We therefore determined if a diet high in omega‐3 fatty acids provided by fish oil can reduce the weight gain and metabolic syndrome phenotype associated chronic high dose glucocorticoid treatment. 3 week old C57BL/6 male mice were fed a “Western type” diet (45% calories from fat (lard) (HFL)) ad libitum. At 6 weeks of age, mice received the synthetic glucocorticoid, Prednisolone, at a dose of 40 mg/m2/day for 28 days. During the Prednisolone treatment, mice either remained on the HFL diet or were switched to an isocaloric diet containing 45% fat from fish oil (HFO). Body weight, food consumption, fat deposition in the liver, accumulation of epididymal adipose tissue and adipocyte size were determined. Mice on the HFO diet gained less weight during the treatment period (P = 0.03), with a dramatic decrease in fat deposition in the liver irrespective of glucocorticoid treatment. Epididymal adipose depots were smaller in mice consuming the HFO diet (P < 0.0001) with a concomitantly decrease in systemic Leptin levels (P = 0.05). Interestingly, glucocorticoid therapy caused a significant increase in adipocyte size when the mice are consuming the HFL diet (P = 0.001). The results from this study suggest that a dietary intervention in the form of fish oil during glucocorticoid treatment can reduce weight gain and metabolic syndrome and reduce long term consequences of ALL treatment.Support or Funding InformationFY16 Faculty Research Grant (University of Memphis)

Glucocorticoids Inhibit Basal and Hormone-Induced Serotonin Synthesis in Pancreatic Beta Cells.

Diabetes is a major complication of chronic Glucocorticoids (GCs) treatment. GCs induce insulin resistance and also inhibit insulin secretion from pancreatic beta cells. Yet, a full understanding of this negative regulation remains to be deciphered. In the present study, we investigated whether GCs could inhibit serotonin synthesis in beta cell since this neurotransmitter has been shown to be involved in the regulation of insulin secretion. To this aim, serotonin synthesis was evaluated in vitro after treatment with GCs of either islets from CD1 mice or MIN6 cells, a beta-cell line. We also explored the effect of GCs on the stimulation of serotonin synthesis by several hormones such as prolactin and GLP 1. We finally studied this regulation in islet in two in vivo models: mice treated with GCs and with liraglutide, a GLP1 analog, and mice deleted for the glucocorticoid receptor in the pancreas. We showed in isolated islets and MIN6 cells that GCs decreased expression and activity of the two key enzymes of serotonin synthesis, Tryptophan Hydroxylase 1 (Tph1) and 2 (Tph2), leading to reduced serotonin contents. GCs also blocked the induction of serotonin synthesis by prolactin or by a previously unknown serotonin activator, the GLP-1 analog exendin-4. In vivo, activation of the Glucagon-like-Peptide-1 receptor with liraglutide during 4 weeks increased islet serotonin contents and GCs treatment prevented this increase. Finally, islets from mice deleted for the GR in the pancreas displayed an increased expression of Tph1 and Tph2 and a strong increased serotonin content per islet. In conclusion, our results demonstrate an original inhibition of serotonin synthesis by GCs, both in basal condition and after stimulation by prolactin or activators of the GLP-1 receptor. This regulation may contribute to the deleterious effects of GCs on beta cells.

Impact of Chronic Glucocorticoid Treatment on Cardiovascular Risk Profile in Patients with Systemic Lupus Erythematosus

Systemic lupus erythematosus is highly associated with premature atherosclerosis and cardiovascular events. The origin of this subclinical atherosclerosis has been attributed mainly to the inflammatory nature of the disease. To assess the effect of long-term use of glucocorticoids on cardiovascular risk in patients with systemic lupus erythematosus. We conducted a registry-based retrospective cohort study. We determined 2 periods: (1) Time 0, that is, time of diagnosis and (2) time 1, that is, when the study was finalized. At both times, the cardiovascular risk was evaluated using the Framingham scale and their scores were compared. Afterward, the change magnitude between the 2 times was evaluated and associated with the cumulative glucocorticoids dose. One hundred one patients were included. The mean ± SD age was 26.5 ± 5 years. Length of disease evolution was of 7.8 ± 4.9 years. There was an 8-point increase in the Framingham score, from -8.1 ± 4 to 0.8 ± 7; P < 0.0001. The correlation between the magnitude of the increase in Framingham score and their corresponding cumulative dose showed a coefficient of 0.88; P < 0.001. The glucocorticoids are a primary factor that influences cardiovascular risk. There is a directly proportional relationship between the cumulative glucocorticoid dose and the increase in cardiovascular risk.

Systemic lupus erythematosus and fractures

Since survival of patients with systemic lupus erythematosus (SLE) has improved over the past decades, increasing attention is focused on complications of the disease. Osteoporosis and fractures contribute to damage...

Recommendations for evaluation and management of bone disease in HIV.

Thirty-four human immunodeficiency virus (HIV) specialists from 16 countries contributed to this project, whose primary aim was to provide guidance on the screening, diagnosis, and monitoring of bone disease in HIV-infected patients. Four clinically important questions in bone disease management were identified, and recommendations, based on literature review and expert opinion, were agreed upon. Risk of fragility fracture should be assessed primarily using the Fracture Risk Assessment Tool (FRAX), without dual-energy X-ray absorptiometry (DXA), in all HIV-infected men aged 40-49 years and HIV-infected premenopausal women aged ≥40 years. DXA should be performed in men aged ≥50 years, postmenopausal women, patients with a history of fragility fracture, patients receiving chronic glucocorticoid treatment, and patients at high risk of falls. In resource-limited settings, FRAX without bone mineral density can be substituted for DXA. Guidelines for antiretroviral therapy should be followed; adjustment should avoid tenofovir disoproxil fumarate or boosted protease inhibitors in at-risk patients. Dietary and lifestyle management strategies for high-risk patients should be employed and antiosteoporosis treatment initiated.

Glucocorticoids as modulators of expression and activity of Antithrombin (At): Potential clinical relevance

IntroductionAn inverse relationship has been reported between decreased postoperative Antithrombin (AT) plasmatic levels and the incidence of complications. We hypothesized that Nuclear Hormone Receptors could modulate the expression of SERPINC1, encoding AT, through a Hormone Regulatory Element present in its promoter, and thus hormone analogs could be a pharmacological complement in surgical procedures to activate endogenous AT synthesis. Materials and MethodsThe expression of SERPINC1 was analyzed in HepG2 cells by quantitative RT-PCR and Western Blot. Two studies were conducted with (a) patients submitted to cardiac surgery with cardiopulmonary bypass receiving (n =17) or not (n=321) glucocorticoids (GCs) as part of their pharmacological treatment, and (b) patients who received (n =20) or not (n=16) GCs as part of their surgery (exodontia or knee arthroscopic, respectively). AT activity in plasma was determined by Innovance Antithrombin Test on a BCS XP System hemostasis analyzer. Results13 nuclear hormone receptor ligands were assayed, being GW4064 (FXR ligand) the most potent activator. Retinoids, activating RXR, and GCs (Dexamethasone, cortisone and methylprednisolone) also resulted in increased AT expression. Chronic GC treatment mitigates the decreased AT activity observed after cardiac surgery. In patients who received two acute GC doses, pre-operative and post-operative AT activity was similar, whereas a significant decrease was observed after surgery in untreated patients. ConclusionsWhereas retinoids and FXR ligands are investigational compounds, regulation of AT by GCS could have a higher potential for translation to clinical practice, pre-conditioning the patient against complications related to reduced AT levels. Larger prospective studies are needed to define the exact role of GCs and their potential clinical utility in cardiac surgery.

Bone health assessment of patients with juvenile idiopathic arthritis: a comparison between DXA and bonexpert

Juvenile idiopathic arthritis (JIA) affects bone mineral density (BMD) due to chronic inflammation, glucocorticoid treatment and immobilization. Dual-energy X-ray absorptiometry (DXA) is most widely used to determine BMD. BoneXpert is a new, feasible and reproducible method for automatic determination of cortical BMD on hand radiographs. Moreover radiation exposure is low and in low-risk peripheral areas.

Coming back

Cachexia is a complex syndrome characterized by body weight loss, tissue wasting, systemic inflammation, metabolic abnormalities, and altered nutritional status. One of the most prominent features of cachexia is the loss of muscle mass, mainly because of increased protein degradation rates. This review is aimed at discussing the involvement of autophagy in the pathogenesis of muscle wasting in cachexia. Modulations of muscle mass in the adult reflect an imbalance between protein synthesis and degradation rates. Muscle depletion in cachexia is associated with increased protein breakdown, mainly involving the pathways dependent on ubiquitin-proteasome and autophagy-lysosomes. This latter, in particular, was considered not relevant for a long time. Just in the last years, autophagy was shown to contribute to the pathogenesis of muscle wasting not only in myopathies because of intrinsic muscle defects, but also in muscle depletion associated with conditions such as sepsis, chronic obstructive pulmonary disease, glucocorticoid treatment, cancer cachexia, and aging. The present review highlights that both excess and defective autophagy are relevant to the onset of muscle depletion, and draws some considerations about possible therapeutic intervention aimed at modulating autophagy in order to improve muscle trophism. http://links.lww.com/COCN/A5.

Chronic glucocorticoid treatment increases de novo lipogenesis in visceral adipose tissue

Chronic glucocorticoid treatment increases <i>de novo</i> lipogenesis in visceral adipose tissue

A transgenic zebrafish model for monitoring glucocorticoid receptor activity

Gene regulation resulting from glucocorticoid receptor and glucocorticoid response element interactions is a hallmark feature of stress response signaling. Imbalanced glucocorticoid production and glucocorticoid receptor activity have been linked to socioeconomically crippling neuropsychiatric disorders, and accordingly there is a need to develop in vivo models to help understand disease progression and management. Therefore, we developed the transgenic SR4G zebrafish reporter line with six glucocorticoid response elements used to promote expression of a short half-life green fluorescent protein following glucocorticoid receptor activation. Herein, we document the ability of this reporter line to respond to both chronic and acute exogenous glucocorticoid treatment. The green fluorescent protein expression in response to transgene activation was high in a variety of tissues including the brain, and provided single-cell resolution in the effected regions. The specificity of these responses is demonstrated using the partial agonist mifepristone and mutation of the glucocorticoid receptor. Importantly, the reporter line also modeled the temporal dynamics of endogenous stress response signaling, including the increased production of the glucocorticoid cortisol following hyperosmotic stress and the fluctuations of basal cortisol concentrations with the circadian rhythm. Taken together, these results characterize our newly developed reporter line for elucidating environmental or genetic modifiers of stress response signaling, which may provide insights to the neuronal mechanisms underlying neuropsychiatric disorders such as major depressive disorder.

Functional dissociation of adult‐born neurons along the dorsoventral axis of the dentate gyrus

Adult-born granule cells in the mammalian dentate gyrus have long been implicated in hippocampal dependent spatial learning and behavioral effects of chronic antidepressant treatment. Although recent anatomical and functional evidence indicates a dissociation of the dorsal and ventral regions of the hippocampus, it is not known if adult neurogenesis within each region specifically contributes to distinct functions or whether adult-born cells along the entire dorsoventral axis are required for these behaviors. We examined the role of distinct subpopulations of adult-born hippocampal granule cells in learning- and anxiety-related behaviors using low-dose focal x-irradiation directed specifically to the dorsal or ventral dentate gyrus. Our findings indicate a functional dissociation between adult-born neurons along the longitudinal axis of the dentate gyrus wherein new neurons in the dorsal dentate gyrus are required for timely acquisition of contextual discrimination while immature neurons in the ventral dentate gyrus are necessary for anxiolytic/antidepressant-related effects of fluoxetine. Interestingly, when contexts are presented with altered temporal cues, or fluoxetine is administered alongside chronic glucocorticoid treatment, this dissociation is abrogated such that adult-born neurons across the entire dorsoventral extent of the dentate gyrus appear to contribute to these behaviors. Our results suggest that individual subpopulations of adult-born hippocampal neurons may be sufficient to mediate distinct behaviors in certain conditions, but are required to act in concert in more challenging situations.

Chronic glucocorticoid treatment enhances lipogenic activity in visceral adipocytes of male Wistar rats

Glucocorticoid (GC) in excess promotes the redistribution of adipose tissue from peripheral to central sites of the body. In this study, we characterized an experimental condition of prolonged GC excess and investigated its effect on the lipogenic metabolism in white adipose tissue. Twenty male Wistar rats were divided into control (CON) and dexamethasone-treated (DEX) groups. DEX group received dexamethasone (0.25 mg kg(-1) day(-1) ) during 4 weeks, while CON group received saline. Animals were killed and subcutaneous (SC), retroperitoneal (RP) and mesenteric (MS) fat pads were excised, weighed and processed for adipocyte isolation, morphometric cell analysis and incorporation of glucose into lipids. The treatment effectively blocked hypothalamic-pituitary-adrenal axis, as verified by a 58% decrease in plasma corticosterone levels and 19% atrophy in adrenal glands in DEX group. Animals from DEX group presented insulin resistance, glucose intolerance, dyslipidaemia and increased insulin and leptin plasma levels and hypertrophied adipocytes. They showed increased lipogenesis in RP and MS depots, with increased incorporation of glucose into fatty acids of triacylglycerol. Increased activity of lipogenic enzymes ATP-citrate lyase, fatty acid synthase, glucose-6-phosphate dehydrogenase and malic was only seen in the MS depot in DEX group, while gene expression of these enzymes was enhanced in SC and MS fat depots. The adaptations promoted by GC treatment in adipose metabolism seemed to be mainly due to the increased activity of enzymes that supply the NADPH required for lipogenesis than to the increase in enzymes that more directly deal with fatty acid synthesis itself.

Nonuremic calciphylaxis precipitated by teriparatide [rhPTH(1–34)] therapy in the setting of chronic warfarin and glucocorticoid treatment

Calciphylaxis occurs rarely in the absence of end stage renal disease. Predisposing factors for nonuremic calciphylaxis (NUC) include hyperparathyroidism, coagulopathies, connective tissue disease, liver disease, glucocorticoid use, and malignancy. Warfarin can facilitate vascular calcification by reducing vitamin K-dependent carboxylation of matrix-Gla proteins. An 86-year-old Caucasian woman with a history of polymyalgia rheumatica, two spontaneous deep venous thromboses (DVTs) and multiple fractures was treated with calcium, vitamin D, prednisone, and warfarin. The patient's low bone density was treated initially with estrogen, then oral bisphosphonate, which was discontinued due to upper gastrointestinal symptoms. Nasal calcitonin was initiated. After 10 years of calcitonin treatment, she was changed to teriparatide. Two months after initiating teriparatide, she developed lower extremity edema and painful erythematous nodular lesions on her calves bilaterally, that progressed to necrotic ulcers despite antibiotic therapy. Biopsy of the lesions showed calcification in the media of small blood vessels and subcutaneous fat with fat necrosis, consistent with calciphylaxis. Teriparatide was discontinued. Aggressive wound care, antibiotics, and intravenous zoledronic acid were initiated. With cessation of teriparatide therapy and intensive wound care, the patient's lesions resolved over 8 months. We report the first case of NUC precipitated by teriparatide therapy. Our patient had multiple underlying predisposing factors including a connective tissue disorder, glucocorticoid therapy, warfarin use, and possible underlying coagulopathy given her history of multiple DVTs. In such patients, alternative osteoporosis therapies may be preferred.

Possible Contribution of Mineralocorticoid Receptor Activation on Glucocorticoid-Induced Left Ventricular Remodeling in Adrenalectomized Rat

Background: Chronic glucocorticoid treatment induces the development of renal injury via mineralocorticoid receptor (MR) activation in bilaterally adrenalectomized rats. It has been hypothesized that glucocorticoid contributes to the development of left ventricular (LV) remodeling through MR activation in bilaterally adrenalectomized rats (ADX). Methods: ADX rats were maintained with 1%NaCl in drinking water and randomly treated as follows for 8 weeks: vehicle (n=7), bilateral adrenalectomy (ADX) + hydrocortisone (HYDRO) (5 mg/kg/day, subcutaneous, n=7), and ADX + HYDRO + eplerenone (0.125% in chow; approximately 75 mg/kg/day, n=7). An osmotic minipump was implanted subcutaneously for continuous infusion of HYDRO. Results: As compared with control vehicletreated uninephrectomized rats, ADX+HYDRO treatment for 8 weeks significantly increased systolic blood pressure, LV weight, collagen content and mRNA levels of atrial natriuretic peptide, brain natriuretic peptide, and collagen type 1 and III. These changes were associated with increase in LV thiobarbituric acid reactive substances content, dihydroethidium fluorescence and mRNA levels of NADPH oxidase subunits. Treatment with a selective MR antagonist, eplerenone significantly attenuated HYDRO induced changes in LV parameters. HYDRO-induced increases in mRNA and protein levels of serum and glucocorticoid-regulated kinases 1 were prevented by eplerenone. Conclusion: These data suggest that chronic glucocorticoid treatment induces LV tissue remodeling through MR dependent mechanism in bilateral adrenalectomized rats. DOI: http://dx.doi.org/10.3329/jbsp.v8i1.16639 J Bangladesh Soc Physiol. 2013, June; 8(1): 6-15

Unmet needs: therapeutic standards of care

Many unmet needs exist for practitioners caring for patients with systemic lupus erythematosus (SLE). The top need is for a blockbuster drug with glucocorticoid efficacy but fewer side effects. They also need better markers to identify responders without waiting 3 to 6 months to see clinical improvement. Current therapeutic goals are to induce and maintain responses while minimizing side effects. Therapy selection varies depending on disease severity and response to previous therapies. Therapies for SLE target different areas in the immunologic process, primarily T-cell and B-cell lymphocytes for mycophenolate mofetil (MMF), azathioprine, and anti-B-lymphocyte stimulator, and a wider array of cells for glucocorticoids. The American College of Rheumatology recently published treatment guidelines for the use of adjunctive therapies in patients with lupus nephritis that recommend hydroxychloroquine as background therapy in all of these patients, and it established target levels for blood pressure, and low-density lipoprotein to reduce complications. Data were inadequate to make recommendations regarding glucocorticoid doses for induction of improvement (thus 0.5 to 1 mg/kg/day is the recommendation) or for tapering or discontinuing prednisone. Renal biopsy is recommended for all patients with active lupus nephritis, previously untreated, to provide data for classification of glomerular disease and thus enable selection of appropriate therapy. Recommendations for induction therapy include either MMF or cyclophosphamide (CYC). MMF has the advantage of being equally effective in all races and being formulated for oral administration. CYC is less effective in African Americans and Latinos but is equivalent in Caucasians and Asians. Low-dose CYC is an option for Caucasians. Teratogenicity is a concern with MMF, CYC, and methotrexate, but hydroxychloroquine, glucocorticoids, and azathioprine can be used during pregnancy, if necessary. New evidence suggests that improvements in proteinuria and C3/C4 blood levels may predict response as early as 8 weeks. Clinical trials with belimumab for lupus nephritis are not yet available although it did not appear to worsen renal disease in patients without active lupus nephritis. Belimumab is approved by the US Food and Drug Administration for use in antinuclear antibodies and/or anti-DNA-positive SLE patients with active disease that persists despite standard treatments. Investigators continue to research other targeted therapies for high response rates, less toxicity, and less need for chronic glucocorticoid treatment. Additional file 1 contains an edited transcript of the full presentation.

AB0064 Spontaneous adipogenesis in bone marrow derived mesenchymal stromal cells after chronic treatment with glucocorticoids

BackgroundMesenchymal stromal cells (MSCs) are a promising therapeutic tool for many inflammatory autoimmune diseases because of their immunosuppressive potential. MSCs autologous transplantation showed less therapeutic efficacy respect to the allogenic...

High dickkopf-1 levels in sera and leukocytes from children with 21-hydroxylase deficiency on chronic glucocorticoid treatment

Searchable abstracts of presentations at key conferences on calcified tissues ISSN 2052-1219 (online)

High dickkopf-1 levels in sera and leukocytes from children with 21-hydroxylase deficiency on chronic glucocorticoid treatment

Children with 21-hydroxylase deficiency (21-OHD) need chronic glucocorticoid (cGC) therapy to replace congenital deficit of cortisol synthesis, and this therapy is the most frequent and severe form of drug-induced osteoporosis. In this study, we enrolled 18 patients (9 females) and 18 sex- and age-matched controls. We found in 21-OHD patients high serum and leukocyte levels of dickkopf-1 (DKK1), a secreted antagonist of the Wnt/β-catenin signaling pathway known to be a key regulator of bone mass. In particular, we demonstrated by flow cytometry, confocal microscopy, and real-time PCR that monocytes, T lymphocytes, and neutrophils from patients expressed high levels of DKK1, which may be related to the cGC therapy. In fact, we showed that dexamethasone treatment markedly induced the expression of DKK1 in a dose- and time-dependent manner in leukocytes. The serum from patients containing elevated levels of DKK1 can directly inhibit in vitro osteoblast differentiation and receptor activator of NF-κB ligand (RANKL) expression. We also found a correlation between both DKK1 and RANKL or COOH-terminal telopeptides of type I collagen (CTX) serum levels in 21-OHD patients on cGC treatment. Our data indicated that DKK1, produced by leukocytes, may contribute to the alteration of bone remodeling in 21-OHD patients on cGC treatment.

Chronic Glucocorticoid Exposure Potentiates Placental Chorionic Plate Artery Constriction: Implications for Aberrant Fetoplacental Vascular Resistance in Fetal Growth Restriction

Fetal growth restriction (FGR) is a serious pregnancy complication, resulting in significant perinatal morbidity and mortality. Increased vascular resistance in the fetoplacental circulation is a hallmark of FGR and is associated with enhanced vasoconstriction of the resistance arteries in the placenta, the chorionic plate arteries (CPAs). Although the cause is unknown, FGR is associated with excess exposure to glucocorticoids (GCs), key mediators of vascular resistance in the systemic circulation. We hypothesized that GCs alter CPA reactivity, thereby contributing to the altered blood flow dynamics seen in FGR. We aimed to examine the acute and chronic effects of GCs on CPA reactivity and the operational mechanisms. Glucocorticoid receptors were highly expressed by CPA. 11β-Hydroxysteroid isoenzyme type 2 was detected within the endothelium, whereas 11β-hydroxysteroid isoenzyme type 1 was absent. Acute GC treatment significantly attenuated U46619-induced constriction. This effect was reversed by cotreatment with mifepristone or an endothelial NOS inhibitor. In contrast, chronic GC treatment potentiated U46619 constriction in a dose-dependent manner, which was partially abolished by mifepristone cotreatment. Similar effects were observed using a novel nonsteroidal glucocorticoid receptor-specific agonist. Chronic treatment with GCs altered the expression of several vasoactive factors, including thromboxane and bradykinin receptors, prokineticin-1, cyclooxygenase-2, and endothelial NOS. In summary, acute and chronic GC treatment exerts contrasting effects on CPA vasoreactivity. These opposing effects are consistent with temporal actions in other vascular beds and reflect activation of distinct nongenomic and genomic pathways. Chronic exposure to elevated GCs may contribute to the raised vascular resistance observed in the fetoplacental circulation in FGR.

Acute and chronic glucocorticoid treatments regulate astrocyte-enriched mRNAs in multiple brain regions in vivo

Previous studies have primarily interpreted gene expression regulation by glucocorticoids in the brain in terms of impact on neurons; however, less is known about the corresponding impact of glucocorticoids on glia and specifically astrocytes in vivo. Recent microarray experiments have identified glucocorticoid-sensitive mRNAs in primary astrocyte cell culture, including a number of mRNAs that have reported astrocyte-enriched expression patterns relative to other brain cell types. Here, we have tested whether elevations of glucocorticoids regulate a subset of these mRNAs in vivo following acute and chronic corticosterone exposure in adult mice. Acute corticosterone exposure was achieved by a single injection of 10 mg/kg corticosterone, and tissue samples were harvested 2 h post-injection. Chronic corticosterone exposure was achieved by administering 10 mg/mL corticosterone via drinking water for 2 weeks. Gene expression was then assessed in two brain regions associated with glucocorticoid action (prefrontal cortex and hippocampus) by qPCR and by in situ hybridization. The majority of measured mRNAs regulated by glucocorticoids in astrocytes in vitro were similarly regulated by acute and/or chronic glucocorticoid exposure in vivo. In addition, the expression levels for mRNAs regulated in at least one corticosterone exposure condition (acute/chronic) demonstrated moderate positive correlation between the two conditions by brain region. In situ hybridization analyses suggest that select mRNAs are regulated by chronic corticosterone exposure specifically in astroctyes based on (1) similar general expression patterns between corticosterone-treated and vehicle-treated animals and (2) similar expression patterns to the pan-astrocyte marker Aldh1l1. Our findings demonstrate that glucocorticoids regulate astrocyte-enriched mRNAs in vivo and suggest that glucocorticoids regulate gene expression in the brain in a cell type-dependent fashion.