Angiotensin II regulates 11β-hydroxysteroid dehydrogenase type 2 via AT2 receptors

Lanz, Bettina; Kadereit, Bert; Ernst, Samuel F.; Shojaati, Kushiar; Causevic, Maja; Frey, Brigitte M.; Frey, Felix J.; Mohaupt, Markus

doi:10.1046/j.1523-1755.2003.00192.x

Cited by 37 publications

(29 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…45,46 ATII decreases the activity of 11␤-HSD2 by an ATII receptordependent and a MAPK-dependent mechanism by inducing a destabilization of 11␤-HSD2 mRNA. 24,47 These observations were made in vitro and await confirmation in vivo. Similarly, the downregulation of 11␤-HSD2 by shear stress, a characteristic of extreme renal vasoconstriction which requires focal adhesion-cytoskeleton interactions, was established in vitro in human cells exhibiting endothelial features.…”

Section: Biology Of 11␤-hsd2mentioning

confidence: 93%

“…23 Two different signal transduction pathways are involved in the regulation of 11␤-HSD2, activation of protein kinase C (PKC) and mitogen-activated protein kinases (MAPKs) or the activation of MAPKs by a PKC-independent pathway. [24][25][26] Bile Acids Inhibit 11␤-HSD2…”

Section: Biology Of 11␤-hsd2mentioning

confidence: 99%

“…32 Pharmacological interventions with beta-blocking agents reduce release of renin, and angiotensin-converting enzyme inhibitors or ATII receptor blocking drugs alleviate ATII-mediated and possibly shear stress-mediated downregulation of 11␤-HSD2. 24,48,66 Whether converting enzyme inhibitors and ATII receptor blockers are useful xenobiotics in some patients with cirrhosis is an unresolved issue. Prevention or aggressive treatment of infection complications, a major cause of the development of hepatorenal syndrome, allows reduction of the release of TNF-␣ or nitric oxide and possibly hypoxemia, 3 mechanisms known to impair 11␤-HSD2 activity.…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

See 2 more Smart Citations

Impaired 11β-hydroxysteroid dehydrogenase contributes to renal sodium avidity in cirrhosis: Hypothesis or fact?

Frey

2006

Hepatology

Self Cite

View full text Add to dashboard Cite

Exaggerated renal sodium retention with concomitant potassium loss is a hallmark of cirrhosis and contributes to the accumulation of fluid as ascites, pleural effusion, or edema. This apparent mineralocorticoid effect is only partially explained by increased aldosterone concentrations. I present evidence supporting the hypothesis that cortisol confers mineralocorticoid action in cirrhosis. The underlying molecular pathology for this mineralocorticoid receptor (MR) activation by cortisol is a reduced activity of the 11␤-hydroxysteroid dehydrogenase type 2, an enzyme protecting the MR from promiscuous activation by cortisol in healthy mammalians. (HEPATOLOGY 2006;44:795-801.) R enal sodium retention and potassium loss are observed in many patients suffering from cirrhosis. Traditionally, this abnormality is attributed to secondary hyperaldosteronism as a consequence of renal hypoperfusion related to intra-abdominal fluid sequestration. 1 This concept has been questioned for 2 reasons. First, patients with cirrhosis accumulating ascites can show renal sodium retention in the presence of normal plasma aldosterone concentration and increased circulating concentrations of natriuretic peptides 2-8 and second, renal sodium retention precedes intra-abdominal fluid sequestration in some situations, and therefore a secondary hyperaldosteronism does not explain the abnormal renal handling of sodium and potassium. 2-4 Many of these patients have a normal renal plasma flow and glomerular filtration rate. Therefore, sodium retention cannot be explained on the basis of an impaired renal perfusion or a decreased filtered sodium load 7 and an unknown mechanism might induce sodium retention. 9 Because this type of renal sodium avidity is linked with enhanced renal potassium loss and blocked by aldosterone antagonists, one is tempted to speculate that the underlying mechanism is an activation of mineralocorticoid receptor (MR). Several independent groups of investigators demonstrated that for a given renal sodium excretion the values for aldosterone were too low in patients with cirrhosis and therefore hypothesized that these findings are explained by an increased renal tubular sensitivity to aldosterone. [10][11][12] Here, the evidence is given for another hypothetical mechanism, which might mimic the presumed increased renal tubular sensitivity to aldosterone, i.e., the presence of a MRactivating ligand other than aldosterone. This ligand is most likely cortisol. MR activation by cortisol is not explained by an enhanced adrenal production rate and/or increased serum concentrations of cortisol in these patients, but by a reduced activity of the enzyme 11␤-hydroxysteroid dehydrogenase type 2 (11␤-HSD2), which allows promiscuous activation of MR by the glucocorticoid cortisol. Activation of MR by CortisolInitially identified in the classic mineralocorticoid-responsive tissues including the aldosterone-sensitive part of the distal nephron, colon, or salivary glands, MR acts as a ligand-inducible transcription factor. 13,14 The cor...

show abstract

Section: Biology Of 11␤-hsd2mentioning

confidence: 93%

Section: Biology Of 11␤-hsd2mentioning

confidence: 99%

Section: Therapeutic Implicationsmentioning

confidence: 99%

See 1 more Smart Citation

Impaired 11β-hydroxysteroid dehydrogenase contributes to renal sodium avidity in cirrhosis: Hypothesis or fact?

Frey

2006

Hepatology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Известно, что кортикостероидные гормоны регулируют экспрессию генов ангиотензиногена, ренина, АПФ, рецепторов ангиотензина, оказывая действие как через системную циркуляцию, так и паракринно, образуясь из своего обратимого метаболита локально в определенных тканях с помощью 11b-гидроксистероиддегидрогеназы (11bГСД) [13]. В свою очередь AII, основной гормон РАС, регулирует как синтез гормонов АКС [14], так и активность 11bГСД [15]. Следовательно, любые изменения функционального состояния этих систем при патологии могут не только прямо, но и опосредованно, через изменение состояния сопряженной системы, влиять на тяжесть патологического процесса и состояние организма в целом.…”

unclassified

Adrenocortical and renin-angiotensin systems in dynamics of experimental diabetes

Черкасова

Selyatitskaya

2013

BIOMED KHIM

View full text Add to dashboard Cite

Исследовали компоненты адренокортикальной системы (содержание кортикостероидных гормонов в надпочечнике, плазме крови и активность 11b-гидроксистероиддегидрогеназы в тканях печени и почек), а также активность важнейшего фермента ренин-ангиотензиновой системы ангиотензинпревращающего фермента в тканях и плазме крови в динамике аллоксанового диабета. Проведенное исследование показало, что в начальный период диабета наблюдается активизация синтеза и секреции в кровь гормонов адренокортикальной системы. Высокий уровень глюкозы и глюкокортикоидных гормонов приводит к увеличению активности ренин-ангиотензиновой системы в лёгких, снижению секреции ангиотензинпревращающего фермента в кровь. При этом активность ренин-ангиотензиновой системы в почках тормозится. Состояние развивающегося диабета приводит к нарушению физиологически обусловленных корреляционных связей между компонентами этих систем. К 30 суткам диабета наблюдаются признаки снижения глюкокортикоидной функции надпочечников, несмотря на сохраняющиеся стойкие нарушения углеводного метаболизма. По-видимому, при этом активность 11b-гидроксистероиддегидрогеназы увеличивается как в надпочечниках, так и в печени, для поддержания высоких уровней основного глюкокортикоидного гормона в крови и тканях. Факторный анализ выявил нарушения межсистемных отношений адренокортикальной и ренин-ангиотензиновой систем при экспериментальном диабете, что свидетельствует о дезинтеграции регуляторных систем.Ключевые слова: кортикостероидные гормоны, 11b-гидроксистероиддегидрогеназа, ангиотензинпревращающий фермент, аллоксановый диабет, высокоэффективная жидкостная хроматография.ВВЕДЕНИЕ. Гормоны и медиаторы адренокортикальной (АКС) и ренин-ангиотензиновой (РАС) систем участвуют в регуляции процессов метаболизма в организме человека и животных. При патологии их функциональное состояние может существенно меняться, что определяется 183 * -адресат для переписки

show abstract

“…Placental ischemia and inflammatory responses during preeclampsia and increased shear stress lead to the release of ATP (9,(25)(26)(27). The cortisol-inactivating enzyme 11␤-HSD2 is highly expressed in trophoblasts and the trophoblast cell line JEG-3 (9,10,22). One important function of the 11␤-HSD2 in placental tissue is to protect the fetus from high maternal cortisol concentrations.…”

mentioning

confidence: 99%

Extracellular ATP Determines 11β-Hydroxysteroid Dehydrogenase Type 2 Activity via Purinergic Receptors

Kadereit

Fustier²,

Shojaati³

et al. 2005

Journal of the American Society of Nephrology

Self Cite

View full text Add to dashboard Cite

Hypertension and sodium retention are features of a diminished 11␤-hydroxysteroid dehydrogenase type 2 (11␤-HSD2). The activity of this enzyme is reduced in various disease states with abnormal renal sodium retention and hypertension, including preeclampsia. ATP release to the extracellular compartment is observed with shear stress, inflammation, and placental ischemia. It was hypothesized that ATP downregulates 11␤-HSD2 activity. For that purpose, cell lines from different tissues that previously were used to study the regulation of 11␤-HSD2 were investigated: JEG-3, a vascular trophoblastic; LLCPK1, a renal tubular; and SW620, a colonic epithelial cell line. The 11␤-HSD2 activity, assessed by the conversion of 3 H-cortisol to cortisone, was reversibly reduced during incubation with ATP or its stable analogue ATP␥S in intact JEG-3 and LLCPK1, but not in SW620 cells. In JEG-3 cells, the purinergic antagonist pyridoxalphosphate-6-azophenyl-2,4-disulphonic acid but not suramin reversed the inhibition. Incubation with UTP and ADP and their degradation products including adenosine and ␣,␤-methylene-ATP did not inhibit 11␤-HSD2 activity. In contrast, 11␤-HSD2 activity increased almost 2.5-fold after incubation with 2-methylthio-ATP. This indicates a bidirectional regulation by nucleotides via purinergic receptors. In JEG-3 cells, ATP/ATP␥S did not alter 11␤-HSD2 promoter activity but reduced 11␤-HSD2 protein and mRNA concentration and half-life, suggesting a posttranscriptional regulation. In conclusion, ATP inhibits cell type specifically via purinergic receptors the expression and activity of the 11␤-HSD2 by a posttranscriptional mechanism.

show abstract

Angiotensin II regulates 11β-hydroxysteroid dehydrogenase type 2 via AT2 receptors

Abstract: Ang II decreases the activity of 11beta-HSD2 by an AT2 receptor- and MAPK-dependent mechanism. The decreased activity of 11beta-HSD2 increases the intracellular availability of cortisol, which might be relevant for the pathogenesis of hypertension and preeclampsia.

Cited by 37 publications

References 41 publications

Impaired 11β-hydroxysteroid dehydrogenase contributes to renal sodium avidity in cirrhosis: Hypothesis or fact?

Impaired 11β-hydroxysteroid dehydrogenase contributes to renal sodium avidity in cirrhosis: Hypothesis or fact?

Adrenocortical and renin-angiotensin systems in dynamics of experimental diabetes

Extracellular ATP Determines 11β-Hydroxysteroid Dehydrogenase Type 2 Activity via Purinergic Receptors

Contact Info

Product

Resources

About