11β-Hydroxysteroid Dehydrogenase

Monder, Carl; White, Perrin C.

doi:10.1016/s0083-6729(08)60447-1

Cited by 200 publications

(93 citation statements)

References 338 publications

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“…Both isoenzymes are to some extent also found in other organs and tissues. [4][5][6][7][8][9] Partial mutation of 11 b-HSD has been reported to cause HT. 10 A genetic defect in the 11 b-HSD enzyme type 2 as in patients with apparent mineralocorticoid excess (AME), as well as inhibition of 11 b-HSD type 2 activity by glycyrrhetinic acid (GA) (the active constituent in liquorice) or carbenoxolone (a synthetic inhibitor), leads to elevated blood pressure (BP), decreased serum potassium concentration, and retention of fluid and sodium, a syndrome of pseudohyperaldosteronism.…”

Section: Introductionmentioning

confidence: 99%

Subjects with essential hypertension are more sensitive to the inhibition of 11 β-HSD by liquorice

et al. 2003

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In this intervention study, we have investigated if hypertensive patients are more sensitive to liquoriceinduced inhibition of 11 b-hydroxysteroid dehydrogenase (11 b-HSD) type 2 than normotensive (NT) subjects and if the response depends on gender. Healthy volunteers and patients with essential hypertension (HT), consumed 100 g of liquorice daily, for 4 weeks, corresponding to a daily intake of 150 mg glycyrrhetinic acid. Office, 24-h ambulatory blood pressure (BP) and blood samples were measured before, during and after liquorice consumption. Effect on cortisol metabolism was evaluated by determining the urinary total cortisol metabolites and urinary free cortisol/free cortisone quotient (Q). The mean rise in systolic BP with office measurements after 4 weeks of liquorice consumption was 3.5 mmHg (po0.06) in NT and 15.3 mmHg (p ¼ 0.003) in hypertensive subjects, the response being different (p ¼ 0.004). The mean rise in diastolic BP was 3.6 mmHg (p ¼ 0.01) in NT and 9.3 mmHg (po0.001) in hypertensive subjects, the response also being different (p ¼ 0.03). Liquorice induced more pronounced clinical symptoms in women than in men (p ¼ 0.0008), although the difference in the effect on the BP was not significant. The increase in Q was prominent (po0.0001) and correlated to the rise in BP (p ¼ 0.02). The rise in BP was not dependant on age, the change in plasma renin activity or weight. We conclude that patients with essential HT are more sensitive to the inhibition of 11 b-HSD by liquorice than NT subjects, and that this inhibition causes more clinical symptoms in women than in men.

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Section: Introductionmentioning

confidence: 99%

Subjects with essential hypertension are more sensitive to the inhibition of 11 β-HSD by liquorice

et al. 2003

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“…11 -HSD is a microsomal enzyme responsible for the interconversion of physiologically active glucocorticoids (cortisol in many species, including sheep and human; corticosterone in rodents) with their inactive 11-keto metabolites (cortisone in many species, including sheep and human; 11-dehydrocorticosterone in rodents), thus regulating the access of active glucocorticoids to their receptors (Monder & White 1993). Two distinct types of 11 -HSD have been cloned and characterized (Rusvai & Naray-Fejes-Toch 1993, Yang & Yu 1994, Brown et al 1996.…”

Section: Introductionmentioning

confidence: 99%

Effects of cortisol and oestradiol on hepatic 11beta-hydroxysteroid dehydrogenase type 1 and glucocorticoid receptor proteins in late-gestation sheep fetus

Gupta¹,

Alfaidy²,

Holloway³

et al. 2003

Journal of Endocrinology

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In the late-gestation sheep, increased fetal plasma cortisol concentration and placental oestradiol (E 2 ) output contribute to fetal organ maturation, in addition to the onset of parturition. Both cortisol and E 2 are believed to regulate the enzyme 11 -hydroxysteroid dehydrogenase type 1 (11 -HSD1), which interconverts bioactive 11-hydroxy glucocorticoids and their inactive 11-keto metabolites. 11 -HSD1, abundantly expressed in fetal liver, operates primarily as a reductase enzyme to produce bioactive cortisol and thus regulates local hepatic glucocorticoid concentrations. Cortisol acts through the glucocorticoid receptor (GR) present in the liver. In this study, we examined the effects of cortisol and E 2 on hepatic 11 -HSD1 and GR in the liver of chronically catheterized sheep fetuses treated with saline (n=5), cortisol (1·35 mg/ h; n=5), saline+4-hydroxyandrostendione, a P450 aromatase inhibitor (4-OHA; 1·44 mg/h; n=5), or cortisol+4-OHA (n=5). Cortisol infusion resulted in increased plasma concentrations of fetal cortisol and E 2 ; concurrent administration of 4-OHA attenuated the increase in plasma E 2 concentrations. Using immunohistochemistry, we showed that fetal hepatocytes expressed both 11 -HSD1 and GR proteins. Cortisol treatment increased GR in both cytosol and nuclei of hepatocytes; concurrent administration of 4-OHA was associated with distinct nuclear GR staining. Western blot revealed that cortisol, in the absence of increased E 2 concentrations, significantly increased concentrations of 11 -HSD1 (34 kDa) and GR (95 kDa) proteins. 11 -HSD1 enzyme activity was measured in the liver microsomal fraction in the presence of [ + (dehydrogenase activity) respectively. 11 -HSD1 reductase activity was significantly greater in the presence of cortisol. In summary, we found that, in sheep during late gestation, cortisol increased both 11 -HSD1 and GR in the fetal liver, and these effects were accentuated in the absence of increased E 2 .

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“…1 However, the enzyme 11␤-hydroxysteroid dehydrogenase type 2 (11BHSD2) protects the mineralocorticoid receptor from the mineralocorticoid actions of cortisol by converting cortisol to cortisone. [2][3][4] Cortisone has a low affinity for the mineralocorticoid receptor 5,6 and aldosterone is therefore the major mineralocorticoid in vivo. The 11BHSD2 gene is located on chromosome 16q22 7 and is expressed at high levels in the kidney, colon and placenta.…”

Section: Introductionmentioning

confidence: 99%

Association between a variant in the 11β-hydroxysteroid dehydrogenase type 2 gene and primary hypertension

et al. 2000

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The enzyme 11␤-hydroxysteroid dehydrogenase type 2 (11BHSD2) converts cortisol to cortisone in the kidney, thereby protecting the mineralocorticoid receptor from the mineralocorticoid actions of cortisol. The syndrome of Apparent Mineralocorticoid Excess (AME), a rare monogenic form of early onset hypertension with autosomal recessive inheritance, is caused by homozygous or compound heterozygous loss of function mutations in the 11BHSD2 gene. Association has been reported between a microsatellite marker flanking the 11BHSD2 gene (D16S496) and primary hypertension. The aim of this study was to identify variants in the 11BHSD2 gene and to test if such variants or the D16S496 are associated with primary hypertension, in Swedes. To address this, the coding sequences of the 11BHSD2 gene was screened for mutations in 20 patients with primary hypertension with single strand conformation polymorphism and direct DNA sequencing techniques. A poly-

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11β-Hydroxysteroid Dehydrogenase

Cited by 200 publications

References 338 publications

Subjects with essential hypertension are more sensitive to the inhibition of 11 β-HSD by liquorice

Subjects with essential hypertension are more sensitive to the inhibition of 11 β-HSD by liquorice

Effects of cortisol and oestradiol on hepatic 11beta-hydroxysteroid dehydrogenase type 1 and glucocorticoid receptor proteins in late-gestation sheep fetus

Association between a variant in the 11β-hydroxysteroid dehydrogenase type 2 gene and primary hypertension

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