Developmental Expression and Glucocorticoid Control of the Leptin Receptor in Fetal Ovine Lung.
The effects of endogenous and synthetic glucocorticoids on fetal lung maturation are well-established, although the role of leptin in lung development before birth is unclear. This study examined mRNA and protein levels of the signalling long-form leptin receptor (Ob-Rb) in fetal ovine lungs towards term, and after experimental manipulation of glucocorticoid levels in utero by fetal cortisol infusion or maternal dexamethasone treatment. In fetal ovine lungs, Ob-Rb protein was localised to bronchiolar epithelium, bronchial cartilage, vascular endothelium, alveolar macrophages and type II pneumocytes. Pulmonary Ob-Rb mRNA abundance increased between 100 (0.69 fractional gestational age) and 144 days (0.99) of gestation, and by 2-4-fold in response to fetal cortisol infusion and maternal dexamethasone treatment. In contrast, pulmonary Ob-Rb protein levels decreased near term and were halved by glucocorticoid treatment, without any significant change in phosphorylated signal transducer and activator of transcription-3 (pSTAT3) at Ser727, total STAT3 or the pulmonary pSTAT3:STAT3 ratio. Leptin mRNA was undetectable in fetal ovine lungs at the gestational ages studied. These findings demonstrate differential control of pulmonary Ob-Rb transcript abundance and protein translation, and/or post-translational processing, by glucocorticoids in utero. Localisation of Ob-Rb in the fetal ovine lungs, including alveolar type II pneumocytes, suggests a role for leptin signalling in the control of lung growth and maturation before birth.
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, United Kingdom.
Miles J
MJ
De Blasio
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, United Kingdom.
Maria
M
Boije
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, United Kingdom.
Owen R
OR
Vaughan
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, United Kingdom.
Brett S
BS
Bernstein
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, United Kingdom.
Katie L
KL
Davies
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, United Kingdom.
Alice
A
Plein
Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom; Department of Obstetrics and Gynaecology, University of Cambridge, The Rosie Hospital, Cambridge, United Kingdom.
Sarah L
SL
Kempster
Department of Obstetrics and Gynaecology, University of Cambridge, The Rosie Hospital, Cambridge, United Kingdom.
Gordon C S
GC
Smith
Department of Obstetrics and Gynaecology, University of Cambridge, The Rosie Hospital, Cambridge, United Kingdom.
D Stephen
DS
Charnock-Jones
School of Animal Biology, University of Western Australia, Perth, Western Australia, Australia.
Dominique
D
Blache
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, United Kingdom.
F B Peter
FB
Wooding
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, United Kingdom.
Dino A
DA
Giussani
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, United Kingdom.
Abigail L
AL
Fowden
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, United Kingdom; Department of Biological and Medical Sciences, Oxford Brookes University, Oxford, United Kingdom.
Alison J
AJ
Forhead
D056809:Alveolar Epithelial Cells / Q000378:metabolism; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005333:Fetus / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D006854:Hydrocortisone / Q000097:blood / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism*; D010766:Phosphorylation; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054411:Receptors, Leptin / Q000235:genetics* / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000737:chemistry / Q000378:metabolism; D034561:Sheep, Domestic; D015398:Signal Transduction
D005938:Glucocorticoids; D012333:RNA, Messenger; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; D003907:Dexamethasone; D006854:Hydrocortisone