Abstract
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.
Highlights
Since identification of the obese gene and its protein product in 1994, and the leptin receptor (Ob-R) in the following year, the physiological functions of leptin in adult life have beenPLOS ONE | DOI:10.1371/journal.pone.0136115 August 19, 2015Glucocorticoids and Lung Leptin Receptors In Utero extensively studied and well-characterised [1, 2, 3]
The long-form leptin receptor Ob-Rb, is the only receptor with the cytoplasmic signalling domain to fully activate a variety of intracellular pathways, including the Janus kinase (JAK) and signal transducers and activators of transcription (STAT) pathway [5]
This study examined the mRNA and protein content of leptin and its long-form receptor (Ob-Rb), and the phosphorylation status of STAT3, in fetal ovine lungs during late gestation, and after experimental manipulation of glucocorticoids by fetal cortisol infusion or by maternal dexamethasone treatment
Summary
Since identification of the obese (ob) gene and its protein product in 1994, and the leptin receptor (Ob-R) in the following year, the physiological functions of leptin in adult life have beenPLOS ONE | DOI:10.1371/journal.pone.0136115 August 19, 2015Glucocorticoids and Lung Leptin Receptors In Utero extensively studied and well-characterised [1, 2, 3]. Since identification of the obese (ob) gene and its protein product in 1994, and the leptin receptor (Ob-R) in the following year, the physiological functions of leptin in adult life have been. Leptin is a polypeptide hormone primarily synthesised and secreted by white adipocytes. It has a key role as a nutritional signal in the regulation of energy intake and expenditure, and in the maintenance of reproductive and immune function [1, 4]. Leptin acts on transmembrane receptors in target cells and there are at least six splice variants of the leptin receptor gene [5]. The long-form leptin receptor Ob-Rb, is the only receptor with the cytoplasmic signalling domain to fully activate a variety of intracellular pathways, including the Janus kinase (JAK) and signal transducers and activators of transcription (STAT) pathway [5]
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