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Journal articles
Lack of Renal 11 Beta-Hydroxysteroid Dehydrogenase type 2 at Birth, a Targeted Temporal Window for Neonatal Glucocorticoid Action in Human and Mice.: Lack of 11βHSD2 activity in newborn kidneys
Abstract : Background Glucocorticoid hormones play a major role in fetal organ maturation. Yet, excessive glucocorticoid exposure in utero can result in a variety of detrimental effects, such as growth retardation and increased susceptibility to the development of hypertension. To protect the fetus, maternal glucocorticoids are metabolized into inactive compounds by placental 11beta-hydroxysteroid dehydrogenase type2 (11βHSD2). This enzyme is also expressed in the kidney, where it prevents illicit occupation of the mineralocorticoid receptor by glucocorticoids. We investigated the role of renal 11βHSD2 in the control of neonatal glucocorticoid metabolism in the human and mouse. Methods Cortisol (F) and cortisone (E) concentrations were measured in maternal plasma, umbilical cord blood and human newborn urine using HPLC. 11βHSD2 activity was indirectly assessed by comparing the F/E ratio between maternal and neonatal plasma (placental activity) and between plasma and urine in newborns (renal activity). Direct measurement of renal 11βHSD2 activity was subsequently evaluated in mice at various developmental stages. Renal 11βHSD2 mRNA and protein expression were analyzed by quantitative RT-PCR and immunohistochemistry during the perinatal period in both species. Results We demonstrate that, at variance with placental 11βHSD2 activity, renal 11βHSD2 activity is weak in newborn human and mouse and correlates with low renal mRNA levels and absence of detectable 11βHSD2 protein. Conclusions We provide evidence for a weak or absent expression of neonatal renal 11βHSD2 that is conserved among species. This temporal and tissue-specific 11βHSD2 expression could represent a physiological window for glucocorticoid action yet may constitute an important predictive factor for adverse outcomes of glucocorticoid excess through fetal programming.
Cited literature [50 references]
https://www.hal.inserm.fr/inserm-00661369
Contributor : Marc Lombes <>
Submitted on : Thursday, January 19, 2012 - 12:49:29 PM
Last modification on : Wednesday, September 16, 2020 - 5:42:14 PM
Long-term archiving on: : Friday, April 20, 2012 - 2:30:15 AM
Contributor : Marc Lombes <>
Submitted on : Thursday, January 19, 2012 - 12:49:29 PM
Last modification on : Wednesday, September 16, 2020 - 5:42:14 PM
Long-term archiving on: : Friday, April 20, 2012 - 2:30:15 AM
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journal.pone.0031949.pdf
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