Abstract | PURPOSE OF REVIEW: RECENT FINDINGS: The determination of the intracellular topology of 11beta-HSD1, facing the endoplasmic reticulum lumen, and 11beta-HSD2, facing the cytoplasm, suggests that 11beta-HSD1 acts as a prereceptor mechanism in the local activation of glucocorticoid receptors, whereas 11beta-HSD2 controls mineralocorticoid receptors by interacting with the receptor in the absence of aldosterone. Downregulation of 11beta-HSD2 was observed with various stimuli including hypoxia, shear stress, angiotensin II and tumor necrosis factor alpha. The corresponding signal transcription pathways and some relevant transcription factors have been identified. Renal sodium retention in liver cirrhosis, nephrotic syndrome and hypoxia have been linked to 11beta-HSD2 reduced activity. Overexpression of 11beta-HSD1 specifically in adipose tissue in mice caused central obesity, a metabolic syndrome and hypertension due to increased intracellular cortisol concentrations. Peroxisome proliferator-activated receptor gamma agonists reduce 11beta-HSD1 activity and diminish the intracellular availability of cortisol, an effect accompanied by a decline in blood pressure. Three individuals with loss-of-function mutations of peroxisome proliferator-activated receptor gamma developed early hypertension. A potential mechanism might be glucocorticoid dependent mineralocorticoid receptor-mediated downregulation of endothelial nitric oxide synthase. SUMMARY:
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Authors | Felix J Frey, A Odermatt, Brigitte M Frey |
Journal | Current opinion in nephrology and hypertension
(Curr Opin Nephrol Hypertens)
Vol. 13
Issue 4
Pg. 451-8
(Jul 2004)
ISSN: 1062-4821 [Print] England |
PMID | 15199296
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
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Chemical References |
- Glucocorticoids
- Receptors, Cytoplasmic and Nuclear
- Receptors, Mineralocorticoid
- Transcription Factors
- 11-beta-Hydroxysteroid Dehydrogenase Type 1
- 11-beta-Hydroxysteroid Dehydrogenase Type 2
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Topics |
- 11-beta-Hydroxysteroid Dehydrogenase Type 1
(physiology)
- 11-beta-Hydroxysteroid Dehydrogenase Type 2
(physiology)
- Glucocorticoids
(pharmacology, physiology)
- Humans
- Hypertension
(physiopathology)
- Receptors, Cytoplasmic and Nuclear
(physiology)
- Receptors, Mineralocorticoid
(drug effects, physiology)
- Transcription Factors
(physiology)
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