11β‐hydroxysteroid dehydrogenase 1 and 2 expression in colon from patients with ulcerative colitis

Žbánková, Šárka; Bryndová, Jana; Leden, Pavel; Kment, Milan; Švec, Alexandr; Pácha, Jiřı́

doi:10.1111/j.1440-1746.2006.04529.x

Cited by 39 publications

(26 citation statements)

References 31 publications

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“…In both ulcerative colitis and in Crohn's disease, 11␤-HSD1 mRNA is increased in the inflamed colon, whereas 11␤-HSD2 mRNA and protein are decreased (802). These effects are replicated by TNF-␣ in colonic tissue explants (186).…”

Section: The Gastrointestinal Tract and Inflammatory Bowel Diseasementioning

confidence: 96%

11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

Chapman

Holmes

Seckl

2013

Physiological Reviews

675

601

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Glucocorticoid action on target tissues is determined by the density of “nuclear” receptors and intracellular metabolism by the two isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD) which catalyze interconversion of active cortisol and corticosterone with inert cortisone and 11-dehydrocorticosterone. 11β-HSD type 1, a predominant reductase in most intact cells, catalyzes the regeneration of active glucocorticoids, thus amplifying cellular action. 11β-HSD1 is widely expressed in liver, adipose tissue, muscle, pancreatic islets, adult brain, inflammatory cells, and gonads. 11β-HSD1 is selectively elevated in adipose tissue in obesity where it contributes to metabolic complications. Similarly, 11β-HSD1 is elevated in the ageing brain where it exacerbates glucocorticoid-associated cognitive decline. Deficiency or selective inhibition of 11β-HSD1 improves multiple metabolic syndrome parameters in rodent models and human clinical trials and similarly improves cognitive function with ageing. The efficacy of inhibitors in human therapy remains unclear. 11β-HSD2 is a high-affinity dehydrogenase that inactivates glucocorticoids. In the distal nephron, 11β-HSD2 ensures that only aldosterone is an agonist at mineralocorticoid receptors (MR). 11β-HSD2 inhibition or genetic deficiency causes apparent mineralocorticoid excess and hypertension due to inappropriate glucocorticoid activation of renal MR. The placenta and fetus also highly express 11β-HSD2 which, by inactivating glucocorticoids, prevents premature maturation of fetal tissues and consequent developmental “programming.” The role of 11β-HSD2 as a marker of programming is being explored. The 11β-HSDs thus illuminate the emerging biology of intracrine control, afford important insights into human pathogenesis, and offer new tissue-restricted therapeutic avenues.

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Section: The Gastrointestinal Tract and Inflammatory Bowel Diseasementioning

confidence: 96%

11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

Chapman

Holmes

Seckl

2013

Physiological Reviews

675

601

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“…Cortisol is metabolized by several enzymes. In the kidney and colon, 11b-hydroxy steroid dehydrogenase type 2 (11b-HSD2) inactivates cortisol to cortisone and thereby protecting the mineralocorticoid receptor from illicit cortisol activation [3,4]. In the liver and adipose tissue, cortisol is regenerated from cortisone by 11b-hydroxy steroid dehydrogenase type 1 (11b-HSD1) which catalyzes predominantly the reverse reductive reaction [5,6].…”

Section: Introductionmentioning

confidence: 99%

11β-hydroxysteroid dehydrogenase type-2 and type-1 (11β-HSD2 and 11β-HSD1) and 5β-reductase activities in the pathogenia of essential hypertension

Campino

Carvajal

Cornejo

et al. 2009

Endocr

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Cortisol availability is modulated by several enzymes: 11β-HSD2, which transforms cortisol (F) to cortisone (E) and 11β-HSD1 which predominantly converts inactive E to active F. Additionally, the A-ring reductases (5α- and 5β-reductase) inactivate cortisol (together with 3α-HSD) to tetrahydrometabolites: 5αTHF, 5βTHF, and THE. The aim was to assess 11β-HSD2, 11β-HSD1, and 5β-reductase activity in hypertensive patients. Free urinary F, E, THF, and THE were measured by HPLC-MS/MS in 102 essential hypertensive patients and 18 normotensive controls. 11β-HSD2 enzyme activity was estimated by the F/E ratio, the activity of 11β-HSD1 in compare to 11β-HSD2 was inferred by the (5αTHF + 5βTHF)/THE ratio and 5β-reductase activity assessed using the E/THE ratio. Activity was considered altered when respective ratios exceeded the maximum value observed in the normotensive controls. A 15.7% of patients presented high F/E ratio suggesting a deficit of 11β-HSD2 activity. Of the remaining 86 hypertensive patients, two possessed high (5αTHF + 5βTHF)/THE ratios and 12.8% had high E/THE ratios. We observed a high percentage of alterations in cortisol metabolism at pre-receptor level in hypertensive patients, previously misclassified as essential. 11β-HSD2 and 5β-reductase decreased activity and imbalance of 11β-HSDs should be considered in the future management of hypertensive patients.

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“…11␤-HSD1 is expressed in many cell types with high levels in liver, adipose and skeletal muscles, and functions in vivo primarily as an oxoreductase to convert inactive 11-ketoglucocorticoids (cortisone in human, 11-dehydrocorticosterone in rodents) to active 11␤-hydroxyglucocorticoids (cortisol in human, corticosterone in rodents) using the cofactor NADPH [10]. 11␤-HSD2 catalyzes the reverse reaction, uses cofactor NAD + and is expressed in mineralocorticoid target tissues like kidney, colon, sweat and salivary glands but also in placenta, inflamed tissue and many tumors and cancer cell lines [11][12][13][14][15][16][17][18][19][20].…”

mentioning

confidence: 99%

Characterization of activity and binding mode of glycyrrhetinic acid derivatives inhibiting 11β-hydroxysteroid dehydrogenase type 2

Kratschmar

Vuorinen

Cunha

et al. 2011

The Journal of Steroid Biochemistry and Molecular Biology

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11β‐hydroxysteroid dehydrogenase 1 and 2 expression in colon from patients with ulcerative colitis

Abstract: Colonic inflammation induces local glucocorticoid activation via 11betaHSD1 and impairs glucocorticoid inactivation via 11betaHSD2. The observed changes indicate a role for local metabolism of glucocorticoids in the control of colonic inflammation.

Cited by 39 publications

References 31 publications

11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

11β-hydroxysteroid dehydrogenase type-2 and type-1 (11β-HSD2 and 11β-HSD1) and 5β-reductase activities in the pathogenia of essential hypertension

Characterization of activity and binding mode of glycyrrhetinic acid derivatives inhibiting 11β-hydroxysteroid dehydrogenase type 2

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