Glucocorticoid metabolism in the developing lung: adrenal-like synthesis pathway

Abstract

Glucocorticoids (GCs) are essential to normal lung development. They participate in the regulation of important developmental events including morphological changes, and lung maturation leading to the surge of surfactant synthesis by type II epithelial cells. Antenatal GC is administered to mothers at risk of premature delivery to reduce the risk of respiratory distress syndrome (RDS). Sex differences were reported in RDS, in the efficiency of antenatal GC treatment independently of surfactant levels, and in surfactant lipid synthesis. Type II epithelial cell maturation is regulated by epithelial-fibroblast cell-cell communication and involves paracrine factors secreted by fibroblasts under the stimulatory effect of GC. This positive action of GC can be inhibited by androgens through the androgen receptor (AR) present in fibroblasts. In fact, lung development is regulated not only by GC and androgens but also by GC and androgen metabolisms within the developing lung. We recently reviewed the metabolism of androgens in the fetal lung [45]. Here, we review multiple aspects of GC metabolism in the developing lung including inactivation and re-activation by 11β-HSDs, synthesis from the adrenal-like synthesis pathway expressed within the lung and the putative role of CRH and ACTH originating from lung in the regulation of this pathway. This article is part of a Special Issue entitled 'Pregnancy and Steroids'.

Keywords: 11β-HSD; 11β-hydroxysteroid dehydrogenase; 17β-HSD; 17β-hydroxysteroid dehydrogenase; 3β-HSD; 3β-hydroxysteroid dehydrogenase/Δ(5)–Δ(4) isomerase; 5α-DH-DOC; 5α-Hydroxy-dehydrocorticosterone; 5α-Reductase; 5α-dihydro-deoxycorticosterone; ACTH; AR; CRH; Corticosteroid; DOC; Deoxycorticosterone; GC; GD; GR; Glucocorticoid receptor; HPA; MC2R; MR; P450scc; PN; PTII; Pomc; Progesterone; RDS; StAR; adrenocorticotropic hormone; androgen receptor; corticotropin-releasing hormone; cytochrome P450 side chain cleavage; deoxycorticosterone; gestation day; glucocorticoid; glucocorticoid receptor; hypothalamic–pituitary–adrenal; melanocortin receptor 2; mineralocorticoid receptor; post-natal day; proopiomelanocortin; respiratory distress syndrome; steroidogenic acute regulatory protein; type II pneumonocytes.