Targeted disruption of the glucocorticoid receptor gene blocks adrenergic chromaffin cell development and severely retards lung maturation

Détails

ID Serval
serval:BIB_5CA884FBE6A0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Targeted disruption of the glucocorticoid receptor gene blocks adrenergic chromaffin cell development and severely retards lung maturation
Périodique
Genes & Development
Auteur(s)
Cole T. J., Blendy J. A., Monaghan A. P., Krieglstein K., Schmid W., Aguzzi A., Fantuzzi G., Hummler E., Unsicker K., Schütz G.
ISSN
0890-9369 (Print)
Statut éditorial
Publié
Date de publication
07/1995
Volume
9
Numéro
13
Pages
1608-21
Notes
Journal Article Research Support, Non-U.S. Gov't --- Old month value: Jul 1
Résumé
The role of the glucocorticoid receptor (GR) in glucocorticoid physiology and during development was investigated by generation of GR-deficient mice by gene targeting. GR -/- mice die within a few hours after birth because of respiratory failure. The lungs at birth are severely atelectatic, and development is impaired from day 15.5 p.c. Newborn livers have a reduced capacity to activate genes for key gluconeogenic enzymes. Feedback regulation via the hypothalamic-pituitary-adrenal axis is severely impaired resulting in elevated levels of plasma adrenocorticotrophic hormone (15-fold) and plasma corticosterone (2.5-fold). Accordingly, adrenal glands are enlarged because of hypertrophy of the cortex, resulting in increased expression of key cortical steroid biosynthetic enzymes, such as side-chain cleavage enzyme, steroid 11 beta-hydroxylase, and aldosterone synthase. Adrenal glands lack a central medulla and synthesize no adrenaline. They contain no adrenergic chromaffin cells and only scattered noradrenergic chromaffin cells even when analyzed from the earliest stages of medulla development. These results suggest that the adrenal medulla may be formed from two different cell populations: adrenergic-specific cells that require glucocorticoids for proliferation and/or survival, and a smaller noradrenergic population that differentiates normally in the absence of glucocorticoid signaling.
Mots-clé
Adrenal Cortex/*embryology/pathology Adrenal Medulla/abnormalities/embryology Animals Animals, Newborn Cell Line Corticosterone/blood Embryo Epinephrine/biosynthesis/deficiency Exons Female Heterozygote Humans Hypertrophy In Situ Hybridization Infant, Newborn Lung/*embryology/pathology/physiology Male Mice Mice, Mutant Strains Pregnancy Receptors, Glucocorticoid/biosynthesis/*genetics/*physiology Recombination, Genetic Reference Values Respiratory Distress Syndrome, Newborn/embryology/*genetics Restriction Mapping Signal Transduction Stem Cells/physiology
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 13:42
Dernière modification de la notice
20/08/2019 15:15
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