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Reproductive Biology and Endocrinology

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Open Access 01-12-2010 | Research

Expression of genes related to the hypothalamic-pituitary-adrenal axis in murine fetal lungs in late gestation

Authors: Marc Simard, Mélissa Côté, Pierre R Provost, Yves Tremblay

Published in: Reproductive Biology and Endocrinology | Issue 1/2010

Abstract

Background

Lung maturation is modulated by several factors, including glucocorticoids. Expression of hypothalamic-pituitary-adrenal (HPA) axis-related components, with proposed or described local regulatory systems analogous to the HPA axis, was reported in peripheral tissues. Here, HPA axis-related genes were studied in the mouse developing lung during a period overlapping the surge of surfactant production.

Methods

Expression of genes encoding for corticotropin-releasing hormone (CRH), CRH receptors (CRHR) 1 and 2beta, CRH-binding protein, proopiomelanocortin (POMC), melanocortin receptor 2 (MC2R), and glucocorticoid receptor was quantified by real-time PCR and localized by in situ hydridization in fetal lungs at gestational days (GD) 15.5, 16.5, and 17.5, and was also quantified in primary mesenchymal- and epithelial cell-enriched cultures. In addition, the capability of CRH and adrenocorticotropic hormone (ACTH) to stimulate pulmonary expression of enzymes involved in the adrenal pathway of glucocorticoid synthesis was addressed, as well as the glucocorticoid production by fetal lung explants.

Results

We report that all the studied genes are expressed in fetal lungs according to different patterns. On GD 15.5, Mc2r showed peaks in expression in samples that have previously presented high mRNA levels for glucocorticoid synthesizing enzymes, including 11beta-hydroxylase (Cyp11b1). Crhr1 mRNA co-localized with Pomc mRNA in cells surrounding the proximal epithelium on GD 15.5 and 16.5. A transition in expression sites toward distal epithelial cells was observed between GD 15.5 and 17.5 for all the studied genes. CRH or ACTH stimulation of genes involved in the adrenal pathway of glucocorticoid synthesis was not observed in lung explants on GD 15.5, whereas CRH significantly increased expression of 21-hydroxylase (Cyp21a1) on GD 17.5. A deoxycorticosterone production by fetal lung explants was observed.

Conclusions

Temporal and spatial modulations of expression of HPA axis-related genes in late gestation are consistent with roles for these genes in lung development. Our data are likely to lead to valuable insights in relation to lung diseases originating from lung immaturity.

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Title: Expression of genes related to the hypothalamic-pituitary-adrenal axis in murine fetal lungs in late gestation
Authors: Marc Simard
Mélissa Côté
Pierre R Provost
Yves Tremblay
Publication date: 01-12-2010
Publisher: BioMed Central
Published in: Reproductive Biology and Endocrinology / Issue 1/2010
Electronic ISSN: 1477-7827
DOI: https://doi.org/10.1186/1477-7827-8-134

At a glance: The STEP trials

Springer Medicine

Expression of genes related to the hypothalamic-pituitary-adrenal axis in murine fetal lungs in late gestation

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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