Human 11β-hydroxysteroid dehydrogenase: Studies on the stably transfected isoforms and localization of the type 2 isozyme within renal tissue

@article{Bujalska1997Human1D,
  title={Human 11$\beta$-hydroxysteroid dehydrogenase: Studies on the stably transfected isoforms and localization of the type 2 isozyme within renal tissue},
  author={Iwona J. Bujalska and Masako Shimojo and Alexander F. Howie and Paul M Stewart},
  journal={Steroids},
  year={1997},
  volume={62},
  pages={77-82}
}
The type 1 and type 2 isoforms of human 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) play a crucial role, respectively, in modulating glucocorticoid and mineralocorticoid hormone action. Deficiency of the 11 beta-HSD2 isoform, as described in the syndrome of apparent mineralocorticoid excess and following liquorice (glycyrrhetinic acid) or carbenoxolone ingestion, results in hypertension in which cortisol acts as a potent mineralocorticoid. Several studies have addressed the effects of… Expand
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References

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Regulation of 11 beta-hydroxysteroid dehydrogenase type 2 activity and mRNA in human choriocarcinoma cells.
TLDR
It is concluded that JEG-3 cells provide an excellent model for further studies on the regulation of 11 beta-HSD2 gene expression in human trophoblast tissue, and that this regulation occurs at a pretranslational level. Expand
Immunohistochemical localization of the 11 beta-hydroxysteroid dehydrogenase type II enzyme in human kidney and placenta.
TLDR
The results suggest that the 11 beta HSD2 enzyme colocalizes with the mineralocorticoid receptor in the distal nephron where it allows aldosterone to occupy its physiological receptor. Expand
Cloning and tissue distribution of the human 1 lβ-hydroxysteroid dehydrogenase type 2 enzyme
TLDR
The isolation of a cDNA coding for human 11 beta HSD2 suggests that 11 betaHSD2 plays an important role in modulating mineralocorticoid and glucoc Corticoid receptor occupancy by glucOCorticoids. Expand
Human kidney 11 beta-hydroxysteroid dehydrogenase is a high affinity nicotinamide adenine dinucleotide-dependent enzyme and differs from the cloned type I isoform.
TLDR
Kinetic analysis of 11 beta HSD activity in human fetal kidney microsomes revealed only a high affinity isoform, the activity of which was exclusively nicotinamide adenine dinucleotide (NAD) dependent, and it seems probable that this isoform is responsible for protecting the renal mineralocorticoid receptor from glucoc Corticoid excess, and a defect in its activity may explain AME. Expand
11 beta-Hydroxysteroid dehydrogenase.
TLDR
Over the 10 years, 11 beta-HSD has progressed from an enzyme merely involved in the peripheral metabolism of cortisol to a crucial pre-receptor signaling pathway in the analysis of corticosteroid hormone action. Expand
Hypertension in the syndrome of apparent mineralocorticoid excess due to mutation of the 11β-hydroxysteroid dehydrogenase type 2 gene
TLDR
The 11 beta-HSD2 gene is analysed as a candidate gene in explaining the molecular basis of AME and a point mutation (C1228T) is found in two affected siblings, and in placental DNA obtained from a stillbirth pregnancy. Expand
Immunolocalization of NAD-dependent 11 beta-hydroxysteroid dehydrogenase in human kidney and colon.
TLDR
The view that the NAD-dependent isoform of 11 beta- HSD (11 beta-HSD2) provides mineralocorticoid specificity by inactivating glucocortioids in an autocrine fashion is supported. Expand
Detection of human 11β-hydroxysteroid dehydrogenase isoforms using reverse-transcriptase-polymerase chain reaction and localization of the type 2 isoform to renal collecting ducts
TLDR
Type 1 and type 2 isoforms of human 11 beta-HSD are expressed in a distinct tissue-specific fashion, in keeping with the proposed differences in their physiological roles. Expand
11 alpha- and 11 beta-hydroxyprogesterone, potent inhibitors of 11 beta-hydroxysteroid dehydrogenase (isoforms 1 and 2), confer marked mineralocorticoid activity on corticosterone in the ADX rat.
TLDR
Both progesterone metabolites were markedly potent in conferring mineralocorticoid activity upon B in the adrenalectomized rat and indicate a possible role for endogenous 11 beta-HSD inhibitors in the regulation of glucoc Corticoid-induced Na+ retention. Expand
The human gene for 11 beta-hydroxysteroid dehydrogenase. Structure, tissue distribution, and chromosomal localization.
TLDR
The data developed in this study should be applicable to the study of patients with hypertension due to apparent mineralocorticoid excess, a deficiency in 11-HSD activity, by hybridization with a previously isolated rat 11- HSD cDNA clone. Expand
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