The bioavailability of glucocorticoids is modulated by enzyme 11β-hydroxysteroid dehydrogenase type 1 (11HSD1), which catalyzes the conversion of inactive 11-oxo-glucocorticoids to active 11-hydroxy-glucocorticoids cortisol and corticosterone and is regulated by pro-inflammatory cytokines. Our aim was to assess the effect of colitis on the expression of 11HSD1 in specific microanatomical compartments of the mucosal immune system. Using qRT-PCR we quantified the expression of 11HSD1 and cytokines in the colon, mesenteric lymph nodes (MLN) and spleen of mice with colitis. Microsamples of the MLN cortex, paracortex and medulla, colonic crypt epithelium (CCE), lamina propria and isolated intestinal lymphoid follicles (ILF) were harvested by laser microdissection, whereas splenic and MLN lymphocytes by flow cytometry. Colitis increased 11HSD1 in the CCE, ILF, and MLN cortex but not in the lamina propria and the MLN paracortex and medulla. Expression of IL-4, IL-21 and TNFα was increased in both the cortex of MLN and ILF, whereas IL-1β and IL-10 were only increased in the follicles. No positive effect was observed in the case of IFNγ and TGFβ. 11HSD1 was positively correlated with TNFα and less strongly with IL-21, IL-1β, and IL-4. Colitis also upregulated the 11HSD1 expression of T cells in the spleen and MLN. The study demonstrates the stimulatory effect of inflammation on local glucocorticoid metabolism only in particular compartments of the mucosal immune system. The correlation between cytokines and 11HSD1 in the ILF and MLN cortex indicates that pro-inflammatory cytokines may amplify glucocorticoid signals in inductive compartments of the mucosal immune system.

• Klíčová slova
• Colon, Cytokine microenvironment, Dextran sodium sulfate colitis, Lymphoid organs, Metabolism of glucocorticoids,
• MeSH
• 11-beta-hydroxysteroiddehydrogenasa typ 1 genetika   metabolismus   MeSH
• cytokiny metabolismus   MeSH
• kolitida enzymologie   genetika   imunologie   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• regulace genové exprese enzymů MeSH
• střevní sliznice imunologie   MeSH
• zánět enzymologie   genetika   imunologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 11-beta-hydroxysteroiddehydrogenasa typ 1 MeSH
• cytokiny MeSH

The aim of the present work was to study the influence of variable stress on the expression of 11β-hydroxysteroid dehydrogenase type 1 (11HSD1) and the neuropeptides corticotropin-releasing hormone (CRH), urocortins 2 and 3(UCN2, UCN3), arginine vasopressin (AVP), oxytocin (OXT) and adenylate cyclase-activating polypeptide (PACAP) in two inbred rat strains: stress hypo-responsive Lewis (LEW) and hyper-responsive Fisher 344 (F344) rats. We found site-specific and strain-dependent differences in the basal and stress-stimulated expression of 11HSD1, CRH, UCN2, UCN3 and PACAP. In LEW rats, stress upregulated 11HSD1 in the prefrontal cortex and lateral amygdala, whereas in F344 rats 11HSD1 was upregulated in the central amygdala and hippocampal CA2 and ventral but not dorsal CA1 region; no effect was observed in the paraventricular nucleus, pituitary gland and adrenal cortex of both strains. The expression of glucocorticoid receptors did not parallel the upregulation of 11HSD1. Stress also stimulated the expression of paraventricular OXT, CRH, UCN3 and PACAP in both strains but amygdalar CRH only in LEW and UCN2/UCN3 in F344 rats, respectively. The upregulation of PACAP and CRH was paralleled only by increased expression of PACAP receptor PAC1 but not CRH receptor type 1. These observations provide evidence that inbred F344 and LEW rats exhibit not only the well-known phenotypic differences in the activity of the HPA axis but also strain- and stress-dependent differences in the expression of genes encoding 11HSD1 and neuropeptides associated with the HPA axis activity. Moreover, the differences in 11HSD1 expression suggest different local concentration of corticosterone and access to GR in canonical and noncanonical structures of the HPA axis.

• Klíčová slova
• 11β-Hydroxysteroid dehydrogenase type 1, Brain, Fisher rat, Lewis rat, Neuropeptides, Stress,
• MeSH
• 11-beta-hydroxysteroiddehydrogenasa typ 1 genetika   metabolismus   MeSH
• amygdala metabolismus   MeSH
• arginin vasopresin genetika   metabolismus   MeSH
• hipokampus metabolismus   MeSH
• hormon uvolňující kortikotropin genetika   metabolismus   MeSH
• hypofýza metabolismus   MeSH
• hypofyzární adenylátcyklázu aktivující peptid genetika   metabolismus   MeSH
• krysa rodu Rattus MeSH
• kůra nadledvin metabolismus   MeSH
• messenger RNA metabolismus   MeSH
• mozek metabolismus   MeSH
• nucleus paraventricularis hypothalami metabolismus   MeSH
• oxytocin genetika   metabolismus   MeSH
• potkani inbrední F344 MeSH
• potkani inbrední LEW MeSH
• prefrontální mozková kůra metabolismus   MeSH
• psychický stres genetika   metabolismus   MeSH
• receptory glukokortikoidů genetika   metabolismus   MeSH
• stanovení celkové genové exprese MeSH
• systém hypofýza - nadledviny metabolismus   MeSH
• systém hypotalamus-hypofýza metabolismus   MeSH
• urokortiny genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• 11-beta-hydroxysteroiddehydrogenasa typ 1 MeSH
• arginin vasopresin MeSH
• hormon uvolňující kortikotropin MeSH
• hypofyzární adenylátcyklázu aktivující peptid MeSH
• messenger RNA MeSH
• oxytocin MeSH
• receptory glukokortikoidů MeSH
• urokortiny MeSH

Multiple lines of evidence suggest the participation of the hippocampus in the feedback inhibition of the hypothalamus-pituitary-adrenal axis during stress response. This inhibition is mediated by glucocorticoid feedback due to the sensitivity of the hippocampus to these hormones. The sensitivity is determined by the expression of glucocorticoid (GR) and mineralocorticoid (MR) receptors and 11beta-hydroxysteroid dehydrogenase type 1 (11HSD1), an enzyme that regulates the conversion of glucocorticoids from inactive to active form. The goal of our study was to assess the effect of stress on the expression of 11HSD1, GR and MR in the ventral and dorsal region of the CA1 hippocampus in three different rat strains with diverse responses to stress: Fisher 344, Lewis and Wistar. Stress stimulated 11HSD1 in the ventral but not dorsal CA1 hippocampus of Fisher 344 but not Lewis or Wistar rats. In contrast, GR expression following stress was decreased in the dorsal but not ventral CA1 hippocampus of all three strains. MR expression was not changed in either the dorsal or ventral CA1 region. These results indicate that (1) depending on the strain, stress stimulates 11HSD1 in the ventral hippocampus, which is known to be involved in stress and emotion reactions whereas (2) independent of strain, stress inhibits GR in the dorsal hippocampus, which is predominantly involved in cognitive functions.

• MeSH
• 11-beta-hydroxysteroiddehydrogenasa typ 1 biosyntéza   genetika   MeSH
• druhová specificita MeSH
• hipokampus metabolismus   MeSH
• krysa rodu Rattus MeSH
• potkani inbrední F344 MeSH
• potkani inbrední LEW MeSH
• potkani Wistar MeSH
• psychický stres genetika   metabolismus   psychologie   MeSH
• steroidní receptory biosyntéza   genetika   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 11-beta-hydroxysteroiddehydrogenasa typ 1 MeSH
• steroidní receptory MeSH

Glucocorticoids exert anti-inflammatory and immunomodulatory effects that may be regulated in part by the activities of the glucocorticoid-activating and -inactivating enzymes, 11β-hydroxysteroid dehydrogenase type 1 (11HSD1) and type 2 (11HSD2), respectively. Previous studies have demonstrated that inflammatory bowel diseases in humans and experimental animals upregulate 11HSD1 and downregulate 11HSD2. We investigated whether proinflammatory cytokines modulate colonic 11HSDs as well as whether lymphoid organs exhibit any 11HSD response to inflammation. Colon tissue explants exposed to tumor necrosis factor α exhibited an upregulation of 11HSD1 mRNA whereas interleukin 1β downregulated 11HSD2 mRNA. Experimental colitis induced by the intracolonic administration of 2,4,6-trinitrobenzenesulfonic acid stimulated 11HSD1 activity not only in the colon but also in mesenteric lymph nodes and the spleen. Analysis of mRNA for 11HSD1 in colon-draining lymph nodes and the spleen showed that inflammation upregulates the expression of this enzyme in mobile lymphoid cells similar to the intraepithelial and lamina propria leukocytes isolated from the colon. It is inferred that inflammation stimulates the reactivation of glucocorticoids in lymphoid organs and in gut-associated lymphoid tissue.

• MeSH
• 11-beta-hydroxysteroiddehydrogenasa typ 1 biosyntéza   genetika   MeSH
• interleukin-1beta farmakologie   MeSH
• kolitida chemicky indukované   enzymologie   MeSH
• kolon účinky léků   MeSH
• krysa rodu Rattus MeSH
• kyselina trinitrobenzensulfonová farmakologie   MeSH
• lymfatické uzliny enzymologie   MeSH
• messenger RNA biosyntéza   genetika   MeSH
• mezenterium MeSH
• potkani Wistar MeSH
• slezina enzymologie   MeSH
• TNF-alfa farmakologie   MeSH
• upregulace MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 11-beta-hydroxysteroiddehydrogenasa typ 1 MeSH
• interleukin-1beta MeSH
• kyselina trinitrobenzensulfonová MeSH
• messenger RNA MeSH
• TNF-alfa MeSH

Glucocorticoids are metabolized in vascular tissue by two types of 11β-hydroxysteroid dehydrogenases (11HSD1, 11HSD2) and thus these enzymes are considered to be important factors that modulate the diverse and complex effects of glucocorticoids on cardiovascular function. The present study evaluated the effect of peroxisome proliferator-activated receptor-γ (PPARγ) agonist pioglitazone on 11HSD1 vascular smooth muscle cells (VSMC) and compared the effect with that of corticosterone. Using primary cultures of VSMC derived from rat aorta, we showed that pioglitazone significantly increases 11HSD1 activity and mRNA expression in a dose-dependent manner with EC(50) 243 nM and that this effect is not blocked by RU 486, an antagonist of the glucocorticoid receptor. In contrast, corticosterone had no effect on 11HSD1. Pioglitazone positively regulated transcription of two CCAAT/enhancer-binding proteins (C/EBPs), specifically C/EBPα a potent activator of 11HSD1 gene transcription in some cells types, and C/EBPζ, whereas C/EBPβ and C/EBPδ were not changed. In contrast, corticosterone stimulated the expression of C/EBPβ and C/EBPδ, but the levels of C/EBPα and C/EBPζ were not changed. In conclusion, activation of PPARγ in VSMC up-regulates vascular 11HSD1 and thus reactivates 11-oxo metabolites to biologically active glucocorticoids through a mechanism that seems to involve C/EBPα and C/EBPζ. Our data provide one of the possible explanations for PPARγ agonists' effects on the cardiovascular system.

• MeSH
• 11-beta-hydroxysteroiddehydrogenasa typ 1 genetika   metabolismus   MeSH
• aktivace enzymů MeSH
• enzymatické testy MeSH
• genetická transkripce MeSH
• kortikosteron farmakologie   MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• myocyty hladké svaloviny účinky léků   enzymologie   MeSH
• pioglitazon MeSH
• potkani Wistar MeSH
• PPAR gama agonisté   metabolismus   MeSH
• svaly hladké cévní cytologie   MeSH
• thiazolidindiony farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 11-beta-hydroxysteroiddehydrogenasa typ 1 MeSH
• 2,4-thiazolidinedione MeSH Prohlížeč
• kortikosteron MeSH
• pioglitazon MeSH
• PPAR gama MeSH
• thiazolidindiony MeSH

11beta-Hydroxysteroid dehydrogenase type 1 (11HSD1) is an enzyme that interconverts active 11-hydroxy glucocorticoids (cortisol, corticosterone) and their inactive 11-oxo derivatives (cortisone, 11-dehydrocorticosterone). Although bidirectional, it is considered to operate in vivo as an 11-reductase that regenerates active glucocorticoids and thus amplifies their local activity in mammals. Here we report the cloning, characterization and tissue distribution of chicken 11HSD1 (ch11HSD1). Its cDNA predicts a protein of 300 amino acids that share 51-56% sequence identity with known mammalian 11HSD1 proteins, while in contrast to most mammals, ch11HSD1 contains only one N-linked glycosylation site. Analysis of the tissue distribution pattern by RT-PCR revealed that ch11HSD1 is expressed in a large variety of tissues, with high expression in the liver, kidney and intestine, and weak in the gonads, brain and heart. 11-Reductase activity has been found in the liver, kidney, intestine and gonads with low or almost zero activity in the brain and heart. These results provide evidence for a role of 11HSD1 as a tissue-specific regulator of glucocorticoid action in non-mammalian vertebrates and may serve as a suitable model for further analysis of 11HSD1 evolution in vertebrates.

• MeSH
• 11-beta-hydroxysteroiddehydrogenasa typ 1 chemie   genetika   metabolismus   MeSH
• glukokortikoidy metabolismus   MeSH
• klonování DNA MeSH
• kur domácí metabolismus   MeSH
• lidé MeSH
• molekulární modely MeSH
• molekulární sekvence - údaje MeSH
• otevřené čtecí rámce MeSH
• sekvence aminokyselin MeSH
• sekvence nukleotidů MeSH
• sekvenční seřazení MeSH
• terciární struktura proteinů MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 11-beta-hydroxysteroiddehydrogenasa typ 1 MeSH
• glukokortikoidy MeSH

Recent in vitro studies have shown the involvement of pro-inflammatory cytokines in the regulation of the local metabolism of glucocorticoids via 11beta-hydroxysteroid dehydrogenase type 1 and type 2 (11HSD1 and 11HSD2). However, direct in vivo evidence for a relationship among the local metabolism of glucocorticoids, inflammation and steroid enzymes is still lacking. We have therefore examined the changes in the local metabolism of glucocorticoids during colonic inflammation induced by TNBS and the consequences of corticosterone metabolism inhibition by carbenoxolone on 11HSD1, 11HSD2, cyclooxygenase 2 (COX-2), mucin 2 (MUC-2), tumor necrosis factor alpha (TNF-alpha), and interleukin 1beta (IL-1beta). The metabolism of glucocorticoids was measured in tissue slices in vitro and their 11HSD1, 11HSD2, COX-2, MUC-2, TNF-alpha, and IL-1beta mRNA abundances by quantitative reverse transcription-polymerase chain reaction. Colitis produced an up-regulation of colonic 11HSD1 and down-regulation of 11HSD2 in a dose-dependent manner, and these changes resulted in a decreased capacity of the inflamed tissue to inactivate tissue corticosterone. Similarly, 11HSD1 transcript was increased in colonic intraepithelial lymphocytes of TNBS-treated rats. Topical intracolonic application of carbenoxolone stimulated 11HSD1 mRNA and partially inhibited 11HSD2 mRNA and tissue corticosterone inactivation and these changes were blocked by RU-486. The administration of budesonide mimicked the effect of carbenoxolone. In contrast to the local metabolism of glucocorticoids, carbenoxolone neither potentiates nor diminishes gene expression for COX-2, TNF-alpha, and IL-1beta, despite the fact that budesonide down-regulated all of them. These data indicate that inflammation is associated with the down-regulation of tissue glucocorticoid catabolism. However, these changes in the local metabolism of glucocorticoids do not modulate the expression of COX-2, TNF-alpha, and IL-1beta in inflamed tissue.

• MeSH
• 11-beta-hydroxysteroiddehydrogenasa typ 1 genetika   metabolismus   MeSH
• 11-beta-hydroxysteroiddehydrogenasa typ 2 genetika   metabolismus   MeSH
• antagonisté hormonů farmakologie   MeSH
• budesonid farmakologie   MeSH
• cyklooxygenasa 2 genetika   metabolismus   MeSH
• glukokortikoidy antagonisté a inhibitory   metabolismus   farmakologie   MeSH
• interleukin-1beta genetika   metabolismus   MeSH
• karbenoxolon farmakologie   MeSH
• kolitida chemicky indukované   metabolismus   MeSH
• kolon účinky léků   enzymologie   metabolismus   MeSH
• kortikosteron metabolismus   MeSH
• krysa rodu Rattus MeSH
• kyselina trinitrobenzensulfonová MeSH
• messenger RNA metabolismus   MeSH
• mifepriston farmakologie   MeSH
• modely nemocí na zvířatech MeSH
• mucin 2 MeSH
• muciny genetika   metabolismus   MeSH
• peroxidasa metabolismus   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• potkani Wistar MeSH
• TNF-alfa genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 11-beta-hydroxysteroiddehydrogenasa typ 1 MeSH
• 11-beta-hydroxysteroiddehydrogenasa typ 2 MeSH
• antagonisté hormonů MeSH
• budesonid MeSH
• cyklooxygenasa 2 MeSH
• glukokortikoidy MeSH
• interleukin-1beta MeSH
• karbenoxolon MeSH
• kortikosteron MeSH
• kyselina trinitrobenzensulfonová MeSH
• messenger RNA MeSH
• mifepriston MeSH
• Muc2 protein, rat MeSH Prohlížeč
• mucin 2 MeSH
• muciny MeSH
• peroxidasa MeSH
• Ptgs2 protein, rat MeSH Prohlížeč
• TNF-alfa MeSH

Corticosteroids have been shown to play a role in cardiac remodeling, with the possibility of a direct effect of overexpression of 11beta-hydroxysteroid dehydrogenase (11HSD) isoform 2 at the level of the cardiomyocytes. The aim of this study was to examine cardiac steroid metabolism in hypertensive rats with hearts that are hypertrophied and fibrotic and have structural alterations in the coronary circulation. To assess possible alterations of cardiac steroid metabolism the expression and activity of both isoforms of 11beta-hydroxysteroid dehydrogenase (11HSD) were studied in spontaneously hypertensive rats (SHR), their normotensive controls Wistar-Kyoto (WKY), and in Dahl salt-sensitive (DS) and salt-resistant rats (DR) kept on a low- or high-salt diet. Using real-time quantitative RT-PCR and enzyme activity assay we found strain-dependent differences in cardiac metabolism of glucocorticoids. In Dahl rats expression of 11HSD1 and 11HSD2 mRNA was lower in DS than in DR rats and was not influenced by dietary salt intake; 11HSD1 mRNA was expressed at higher level than 11HSD2 mRNA. NADP(+)-dependent cardiac 11HSD activity showed similar distribution as 11HSD1 mRNA-lower activity in DS than in DR rats and no effect of salt intake. In SHR and WKY strains 11HSD2 mRNA expression was significantly higher in WKY than in SHR but no differences were observed in 11HSD1 mRNA abundance and NADP(+)-dependent 11HSD activity. These results show that the heart is able to metabolize glucocorticoids and that this metabolism is strain-dependent but do not support the notion of association between cardiac hypertrophy and changes of 11HSD1 and 11HSD2 expression.

• MeSH
• 11-beta-hydroxysteroiddehydrogenasa typ 1 genetika   metabolismus   MeSH
• dieta s nízkým obsahem soli MeSH
• fenotyp MeSH
• glukokortikoidy metabolismus   MeSH
• hypertenze enzymologie   MeSH
• kardiomegalie enzymologie   MeSH
• kinetika MeSH
• krysa rodu Rattus MeSH
• messenger RNA genetika   MeSH
• myokard enzymologie   MeSH
• potkani inbrední Dahl MeSH
• potkani inbrední SHR MeSH
• potkani inbrední WKY MeSH
• referenční hodnoty MeSH
• regulace genové exprese enzymů MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 11-beta-hydroxysteroiddehydrogenasa typ 1 MeSH
• glukokortikoidy MeSH
• messenger RNA MeSH

Glucocorticoid hormones have been reported to operate as regulators of cell proliferation and differentiation and to inhibit growth of several colon tumors and adenocarcinoma cell lines. The glucocorticoid action is regulated, in part, at the pre-receptor level through the expression of isoforms of 11beta-hydroxysteroid dehydrogenase (11betaHSD1, 11betaHSD2) which are responsible for the interconversion of hormonally active cortisol to cortisone. Since both of these isoforms are expressed in the mammalian colon, we examined whether 11betaHSD1 and 11betaHSD2 are expressed in human colorectal cancer and whether their expression differs between neoplastic and autologous non-neoplastic tissue. We provide evidence that both isoforms of 11betaHSD are expressed in the colon adenocarcinoma, but their expression is not identical in neoplastic and non-neoplastic tissue. There is a significant decrease of 11betaHSD2 mRNA abundance and enzyme activity in neoplastic tissue. In contrast, 11betaHSD1 activity and mRNA abundance are increased in some but not all tumor samples. The results demonstrate that (1) neoplastic transformation is associated with decreasing steady-state levels of 11betaHSD2 mRNA and enzyme activity and in some cases also with increasing expression of 11betaHSD1, and (2) colorectal tumor cells have a decreased capability of autocrine inactivation of glucocorticoids.

• MeSH
• 11-beta-hydroxysteroiddehydrogenasa typ 1 genetika   metabolismus   MeSH
• 11-beta-hydroxysteroiddehydrogenasa typ 2 genetika   metabolismus   MeSH
• adenokarcinom enzymologie   genetika   patologie   MeSH
• hydrokortison metabolismus   MeSH
• izoenzymy genetika   MeSH
• kolorektální nádory enzymologie   genetika   patologie   MeSH
• kortison metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA genetika   metabolismus   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• 11-beta-hydroxysteroiddehydrogenasa typ 1 MeSH
• 11-beta-hydroxysteroiddehydrogenasa typ 2 MeSH
• hydrokortison MeSH
• izoenzymy MeSH
• kortison MeSH
• messenger RNA MeSH

BACKGROUND: Pro-inflammatory processes are counteracted by anti-inflammatory factors such as glucocorticoids. The response of target cells to glucocorticoids depends on several factors including prereceptor modulation of glucocorticoid signals via local glucocorticoid metabolism. This is determined by two isoforms of 11beta-hydroxysteroid dehydrogenase (11betaHSD); 11betaHSD1 operates in vivo as a reductase converting inactive 11-oxo glucocorticoids to active glucocorticoids cortisol or corticosterone, whereas 11betaHSD2 catalyses oxidation of active glucocorticoids to their inactive 11-oxo derivatives. The aim of this study was to investigate the changes in local metabolism of glucocorticoids and in the expression of 11betaHSD1 and 11betaHSD2 mRNA during colonic inflammation. METHODS: Acute colitis was induced by intracolonic administration of 2,4,6-trinitrobenzenesulphonic acid (TNBS) or by drinking a dextran sodium sulphate (DSS) solution. Metabolism of glucocorticoids was measured in tissue fragments in vitro and 11betaHSD1 and 11betaHSD2 mRNA abundance was quantified using real-time RT-PCR one week after administration of TNBS and 10 days after drinking the DSS solution. RESULTS: In both models of inflammatory bowel disease we observed down-regulation of corticosterone oxidation to 11-dehydrocorticosterone by 64% (TNBS) and 53% (DSS) and reciprocal stimulation of reduction of 11-dehydrocorticosterone to corticosterone by 83% and 54%, respectively. A similar pattern was observed at the level of mRNA; 11betaHSD1 mRNA was significantly higher (TNBS: increase by 660%; DSS: increase by 760%) and 11betaHSD2 mRNA lower (TNBS: decrease by 85%; DSS: decrease by 60%) during inflammation. CONCLUSIONS: Colitis induces local glucocorticoid activation from 11-oxo steroids and decreases glucocorticoid inactivation; i.e. inflammation increases local tissue ratio of active and inactive glucocorticoids. The results indicate that the changes in local metabolism of glucocorticoids could contribute to the control of an overshoot of inflammation processes in the colon.

• MeSH
• 11-beta-hydroxysteroiddehydrogenasa typ 1 genetika   metabolismus   MeSH
• 11-beta-hydroxysteroiddehydrogenasa typ 2 genetika   metabolismus   MeSH
• Crohnova nemoc chemicky indukované   enzymologie   MeSH
• kortikosteron analogy a deriváty   metabolismus   MeSH
• krysa rodu Rattus MeSH
• kyselina trinitrobenzensulfonová MeSH
• messenger RNA genetika   MeSH
• modely nemocí na zvířatech MeSH
• potkani Wistar MeSH
• síran dextranu MeSH
• ulcerózní kolitida chemicky indukované   enzymologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 11-beta-hydroxysteroiddehydrogenasa typ 1 MeSH
• 11-beta-hydroxysteroiddehydrogenasa typ 2 MeSH
• 11-dehydrocorticosterone MeSH Prohlížeč
• kortikosteron MeSH
• kyselina trinitrobenzensulfonová MeSH
• messenger RNA MeSH
• síran dextranu MeSH