Developmental expression and glucocorticoid control of the leptin receptor in fetal ovine lung

Miles J. De Blasio, Maria Boije, Owen R. Vaughan, Brett S. Bernstein, Katie L. Davies, Alice Plein, Sarah L. Kempster, Gordon C.S. Smith, D. Stephen Charnock-Jones, Dominique Blache, F. B.Peter Wooding, Dino A. Giussani, Abigail L. Fowden, Alison J. Forhead

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The effects of endogenous and synthetic glucocorticoids on fetal lung maturation are wellestablished, 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 ormaternal 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. LeptinmRNA 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.

Original languageEnglish
Article numbere0136115
Number of pages15
JournalPLoS ONE
Issue number8
Publication statusPublished - 19 Aug 2015
Externally publishedYes

Cite this

De Blasio, M. J., Boije, M., Vaughan, O. R., Bernstein, B. S., Davies, K. L., Plein, A., Kempster, S. L., Smith, G. C. S., Charnock-Jones, D. S., Blache, D., Wooding, F. B. P., Giussani, D. A., Fowden, A. L., & Forhead, A. J. (2015). Developmental expression and glucocorticoid control of the leptin receptor in fetal ovine lung. PLoS ONE, 10(8), [e0136115].