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Is the Fetal Lung a Mineralocorticoid Receptor Target Organ? Induction of Cortisol-Regulated Genes in the Ovine Fetal Lung, Kidney and Small Intestine
BACKGROUND: Lung, kidney and small intestine are involved in fetal volume regulation and amniotic fluid secretion and play a pivotal role in the transition from intrauterine to extrauterine life. Objective: This study was performed to determine the ontogeny of mineralocorticoid receptors (MR) and gl...
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Formato: | Texto |
Lenguaje: | English |
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S. Karger AG
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654587/ https://www.ncbi.nlm.nih.gov/pubmed/18787337 http://dx.doi.org/10.1159/000151755 |
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author | Keller-Wood, Maureen von Reitzenstein, Marcela McCartney, Jarret |
author_facet | Keller-Wood, Maureen von Reitzenstein, Marcela McCartney, Jarret |
author_sort | Keller-Wood, Maureen |
collection | PubMed |
description | BACKGROUND: Lung, kidney and small intestine are involved in fetal volume regulation and amniotic fluid secretion and play a pivotal role in the transition from intrauterine to extrauterine life. Objective: This study was performed to determine the ontogeny of mineralocorticoid receptors (MR) and glucocorticoid receptors (GR), and of MR- and GR-regulated genes and proteins, serum and glucocorticoid-induced kinase (Sgk-1), epithelial sodium channel (ENaCα), and Na,K-ATPase α1. METHODS: Lung, renal cortex and medulla, and small intestine were collected from fetuses at 80, 100, 120, 130 and 145 days’ gestation and from day 1 and 7 neonatal lambs. Real-time PCR was performed to determine mRNA concentration for MR, GR, the 11β-hydroxysteroid dehydrogenases (11β-HSD1 and 2), Sgk-1, ENaCα, and Na,K-ATPase α1. Protein expression of ENaCα and Na,K-ATPase α1 in whole cell and membrane fractions was determined by immunoblotting. RESULTS: Expression of corticosteroid-induced genes in renal cortex increases at term; in small intestine the induction occurs postnatally. In contrast, in lung expression of MR and GR mRNAs were greater at 100 days to term than postnatally and 11β-HSD1 peaked at 145 days; the corticosteroid-induced genes also increased prenatally: Sgk-1 and ENaCα increased by 120 days, peaking at 145 days, and Na,K-ATPase α1 was greatest at 130 days. CONCLUSIONS: The expression of high levels of MR and 11β-HSD1 in preterm fetal lung suggest low endogenous fetal cortisol may exert actions at the high affinity MR in vivo, leading to increases in expression of sodium channels important in the regulation of lung liquid secretion and reabsorption. |
format | Text |
id | pubmed-2654587 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | S. Karger AG |
record_format | MEDLINE/PubMed |
spelling | pubmed-26545872010-01-01 Is the Fetal Lung a Mineralocorticoid Receptor Target Organ? Induction of Cortisol-Regulated Genes in the Ovine Fetal Lung, Kidney and Small Intestine Keller-Wood, Maureen von Reitzenstein, Marcela McCartney, Jarret Neonatology Original Paper BACKGROUND: Lung, kidney and small intestine are involved in fetal volume regulation and amniotic fluid secretion and play a pivotal role in the transition from intrauterine to extrauterine life. Objective: This study was performed to determine the ontogeny of mineralocorticoid receptors (MR) and glucocorticoid receptors (GR), and of MR- and GR-regulated genes and proteins, serum and glucocorticoid-induced kinase (Sgk-1), epithelial sodium channel (ENaCα), and Na,K-ATPase α1. METHODS: Lung, renal cortex and medulla, and small intestine were collected from fetuses at 80, 100, 120, 130 and 145 days’ gestation and from day 1 and 7 neonatal lambs. Real-time PCR was performed to determine mRNA concentration for MR, GR, the 11β-hydroxysteroid dehydrogenases (11β-HSD1 and 2), Sgk-1, ENaCα, and Na,K-ATPase α1. Protein expression of ENaCα and Na,K-ATPase α1 in whole cell and membrane fractions was determined by immunoblotting. RESULTS: Expression of corticosteroid-induced genes in renal cortex increases at term; in small intestine the induction occurs postnatally. In contrast, in lung expression of MR and GR mRNAs were greater at 100 days to term than postnatally and 11β-HSD1 peaked at 145 days; the corticosteroid-induced genes also increased prenatally: Sgk-1 and ENaCα increased by 120 days, peaking at 145 days, and Na,K-ATPase α1 was greatest at 130 days. CONCLUSIONS: The expression of high levels of MR and 11β-HSD1 in preterm fetal lung suggest low endogenous fetal cortisol may exert actions at the high affinity MR in vivo, leading to increases in expression of sodium channels important in the regulation of lung liquid secretion and reabsorption. S. Karger AG 2008-12 2008-09-12 /pmc/articles/PMC2654587/ /pubmed/18787337 http://dx.doi.org/10.1159/000151755 Text en Copyright © 2008 by S. Karger AG, Basel http://www.karger.com/Authors_Choice This is an open access article distributed under the terms of Karger's Author's Choice™ licensing agreement, adapted from the Creative Commons Attribution Non-Commercial 2.5 license. This license allows authors to re-use their articles for educational and research purposes as long as the author and the journal are fully acknowledged. |
spellingShingle | Original Paper Keller-Wood, Maureen von Reitzenstein, Marcela McCartney, Jarret Is the Fetal Lung a Mineralocorticoid Receptor Target Organ? Induction of Cortisol-Regulated Genes in the Ovine Fetal Lung, Kidney and Small Intestine |
title | Is the Fetal Lung a Mineralocorticoid Receptor Target Organ? Induction of Cortisol-Regulated Genes in the Ovine Fetal Lung, Kidney and Small Intestine |
title_full | Is the Fetal Lung a Mineralocorticoid Receptor Target Organ? Induction of Cortisol-Regulated Genes in the Ovine Fetal Lung, Kidney and Small Intestine |
title_fullStr | Is the Fetal Lung a Mineralocorticoid Receptor Target Organ? Induction of Cortisol-Regulated Genes in the Ovine Fetal Lung, Kidney and Small Intestine |
title_full_unstemmed | Is the Fetal Lung a Mineralocorticoid Receptor Target Organ? Induction of Cortisol-Regulated Genes in the Ovine Fetal Lung, Kidney and Small Intestine |
title_short | Is the Fetal Lung a Mineralocorticoid Receptor Target Organ? Induction of Cortisol-Regulated Genes in the Ovine Fetal Lung, Kidney and Small Intestine |
title_sort | is the fetal lung a mineralocorticoid receptor target organ? induction of cortisol-regulated genes in the ovine fetal lung, kidney and small intestine |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654587/ https://www.ncbi.nlm.nih.gov/pubmed/18787337 http://dx.doi.org/10.1159/000151755 |
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