Placental 11β-hydroxysteroid dehydrogenase activity in normotensive and pre-eclamptic pregnancies

Mccalla, C. O.; Nacharaju, Vijaya L.; Muneyyirci-Delale, Ozgul; Glasgow, Sandra; Feldman, Joseph

doi:10.1016/s0039-128x(98)00056-7

Cited by 96 publications

(61 citation statements)

References 24 publications

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“…The placental 11b-HSD-type2 seems to have a regulatory effect on feto±placental growth and differentiation, supported by a direct correlation between 11b-HSD activity and birth weight and an inverse relation between 11b-HSD and placenta weight (93,94). The hypothesis derived from these findings suggests that higher GC levels during fetal life, due to an impaired activity of placental 11b-HSD-type2, could lead to programming of hypertension in adult life (95±97).…”

Section: Essential' Hypertensionmentioning

confidence: 96%

Clinical implications of glucocorticoid metabolism by 11beta-hydroxysteroid dehydrogenases in target tissues

Quinkler

Oelkers²,

Diederich³

2001

European Journal of Endocrinology

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11b-Hydroxysteroid dehydrogenases (11b-HSD) are microsomal enzymes that catalyze the conversion of active glucocorticoids (GC) to their inactive 11-dehydro products and vice versa. Two isoenzymes of 11b-HSD have been characterized and cloned in human tissues. The tissue-specific metabolism of GC by these enzymes is important for mineralocorticoid (MC) and GC receptor occupancy and seems to play a crucial role in the pathogenesis of diseases such as apparent MC excess syndrome, and may play roles in hypertension, obesity and impaired hepatic glucose homeostasis. This article reviews the literature and examines the role and importance of 11b-HSD in humans.

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Section: Essential' Hypertensionmentioning

confidence: 96%

Clinical implications of glucocorticoid metabolism by 11beta-hydroxysteroid dehydrogenases in target tissues

Quinkler

Oelkers²,

Diederich³

2001

European Journal of Endocrinology

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“…Hypertension in low protein model also was glucocorticoid dependent as maternal adrenalectomy significantly reduced the blood pressure to control levels and corticosterone replacement restored the hypertensive state seen these exposed offspring (151). In human, the placental 11 β-HSD 2 activity correlated with birth weight (184) and reduced in pre-eclampsia (185) and in intrauterine growth restricted fetuses (186). Moreover, 11 β-HSD 2 gene mutation constantly resulted in lower fetal birth weight compared to normal human fetus (187).…”

Section: Glucocorticoids Over Exposurementioning

confidence: 99%

Glucocorticoids: Biochemical Group That Play Key Role in Fetal Programming of Adult Disease

Erhuma¹

2012

Glucocorticoids - New Recognition of Our Familiar Friend

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“…Placental lesions such as arteriolopathy, hypermaturity of villi, intervillous thrombi, and central infarction are more frequent and severe in preeclampsia, a disease characterized by hypertension and renal damage with proteinuria (22)(23)(24). Placental ischemia and inflammatory responses during preeclampsia and increased shear stress lead to the release of ATP (9,(25)(26)(27).…”

mentioning

confidence: 99%

“…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%

“…The reduction of 11␤-HSD2 activity in the presence of high ATP levels observed in preeclampsia (22,23) prompted us to determine whether ATP might contribute to a reduced 11␤-HSD2 activity in trophoblasts and to elucidate whether intact cells are needed to modulate the 11␤-HSD2 activity by extracellular mononucleotides. To explore this hypothesis, we investigated the well-characterized human choriocarcinoma cell line JEG-3 displaying endothelial properties and two cell lines with epithelial features: LLCPK1, a renal tubular, and SW620, a human colonic cell line.…”

mentioning

confidence: 99%

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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

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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.

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Placental 11β-hydroxysteroid dehydrogenase activity in normotensive and pre-eclamptic pregnancies

Cited by 96 publications

References 24 publications

Clinical implications of glucocorticoid metabolism by 11beta-hydroxysteroid dehydrogenases in target tissues

Clinical implications of glucocorticoid metabolism by 11beta-hydroxysteroid dehydrogenases in target tissues

Glucocorticoids: Biochemical Group That Play Key Role in Fetal Programming of Adult Disease

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

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