title: Leptin Matures Aspects of Lung Structure and Function in the Ovine Fetus.
abstract: In human and ovine fetuses, glucocorticoids stimulate leptin secretion, although the extent to which leptin mediates the maturational effects of glucocorticoids on pulmonary development is unclear. This study investigated the effects of leptin administration on indices of lung structure and function before birth. Chronically catheterized singleton sheep fetuses were infused iv for 5 days with either saline or recombinant ovine leptin (0.5 mg/kg · d leptin (LEP), 0.5 LEP or 1.0 mg/kg · d, 1.0 LEP) from 125 days of gestation (term ∼145 d). Over the infusion, leptin administration increased plasma leptin, but not cortisol, concentrations. On the fifth day of infusion, 0.5 LEP reduced alveolar wall thickness and increased the volume at closing pressure of the pressure-volume deflation curve, interalveolar septal elastin content, secondary septal crest density, and the mRNA abundance of the leptin receptor (Ob-R) and surfactant protein (SP) B. Neither treatment influenced static lung compliance, maximal lung volume at 40 cmH2O, lung compartment volumes, alveolar surface area, pulmonary glycogen, protein content of the long form signaling Ob-Rb or phosphorylated signal transducers and activators of transcription-3, or mRNA levels of SP-A, C, or D, elastin, vascular endothelial growth factor-A, the vascular endothelial growth factor receptor 2, angiotensin-converting enzyme, peroxisome proliferator-activated receptor γ, or parathyroid hormone-related peptide. Leptin administration in the ovine fetus during late gestation promotes aspects of lung maturation, including up-regulation of SP-B.
authors.affiliation: Department of Physiology, Development and Neuroscience (M.J.D.B., M.B., A.D., A.H., F.B.P.W., A.L.F., A.J.F.), University of Cambridge, Cambridge CB2 3EG, United Kingdom; Department of Medicine (S.L.K.), University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Department of Obstetrics and Gynaecology (G.C.S.S., D.S.C.-J.), University of Cambridge, The Rosie Hospital, Cambridge CB2 0SW, United Kingdom; School of Animal Biology (D.B.), University of Western Australia, Crawley, Perth, Western Australia, Australia 60095; and Department of Biological and Medical Sciences (A.J.F.), Oxford Brookes University, Oxford OX3 0BP, United Kingdom.
authors.forename: Miles J
authors.initials: MJ
authors.lastname: De Blasio
authors.affiliation: Department of Physiology, Development and Neuroscience (M.J.D.B., M.B., A.D., A.H., F.B.P.W., A.L.F., A.J.F.), University of Cambridge, Cambridge CB2 3EG, United Kingdom; Department of Medicine (S.L.K.), University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Department of Obstetrics and Gynaecology (G.C.S.S., D.S.C.-J.), University of Cambridge, The Rosie Hospital, Cambridge CB2 0SW, United Kingdom; School of Animal Biology (D.B.), University of Western Australia, Crawley, Perth, Western Australia, Australia 60095; and Department of Biological and Medical Sciences (A.J.F.), Oxford Brookes University, Oxford OX3 0BP, United Kingdom.
authors.forename: Maria
authors.initials: M
authors.lastname: Boije
authors.affiliation: Department of Physiology, Development and Neuroscience (M.J.D.B., M.B., A.D., A.H., F.B.P.W., A.L.F., A.J.F.), University of Cambridge, Cambridge CB2 3EG, United Kingdom; Department of Medicine (S.L.K.), University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Department of Obstetrics and Gynaecology (G.C.S.S., D.S.C.-J.), University of Cambridge, The Rosie Hospital, Cambridge CB2 0SW, United Kingdom; School of Animal Biology (D.B.), University of Western Australia, Crawley, Perth, Western Australia, Australia 60095; and Department of Biological and Medical Sciences (A.J.F.), Oxford Brookes University, Oxford OX3 0BP, United Kingdom.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Kempster
authors.affiliation: Department of Physiology, Development and Neuroscience (M.J.D.B., M.B., A.D., A.H., F.B.P.W., A.L.F., A.J.F.), University of Cambridge, Cambridge CB2 3EG, United Kingdom; Department of Medicine (S.L.K.), University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Department of Obstetrics and Gynaecology (G.C.S.S., D.S.C.-J.), University of Cambridge, The Rosie Hospital, Cambridge CB2 0SW, United Kingdom; School of Animal Biology (D.B.), University of Western Australia, Crawley, Perth, Western Australia, Australia 60095; and Department of Biological and Medical Sciences (A.J.F.), Oxford Brookes University, Oxford OX3 0BP, United Kingdom.
authors.forename: Gordon C S
authors.initials: GC
authors.lastname: Smith
authors.affiliation: Department of Physiology, Development and Neuroscience (M.J.D.B., M.B., A.D., A.H., F.B.P.W., A.L.F., A.J.F.), University of Cambridge, Cambridge CB2 3EG, United Kingdom; Department of Medicine (S.L.K.), University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Department of Obstetrics and Gynaecology (G.C.S.S., D.S.C.-J.), University of Cambridge, The Rosie Hospital, Cambridge CB2 0SW, United Kingdom; School of Animal Biology (D.B.), University of Western Australia, Crawley, Perth, Western Australia, Australia 60095; and Department of Biological and Medical Sciences (A.J.F.), Oxford Brookes University, Oxford OX3 0BP, United Kingdom.
authors.forename: D Stephen
authors.initials: DS
authors.lastname: Charnock-Jones
authors.affiliation: Department of Physiology, Development and Neuroscience (M.J.D.B., M.B., A.D., A.H., F.B.P.W., A.L.F., A.J.F.), University of Cambridge, Cambridge CB2 3EG, United Kingdom; Department of Medicine (S.L.K.), University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Department of Obstetrics and Gynaecology (G.C.S.S., D.S.C.-J.), University of Cambridge, The Rosie Hospital, Cambridge CB2 0SW, United Kingdom; School of Animal Biology (D.B.), University of Western Australia, Crawley, Perth, Western Australia, Australia 60095; and Department of Biological and Medical Sciences (A.J.F.), Oxford Brookes University, Oxford OX3 0BP, United Kingdom.
authors.forename: Alice
authors.initials: A
authors.lastname: Denyer
authors.affiliation: Department of Physiology, Development and Neuroscience (M.J.D.B., M.B., A.D., A.H., F.B.P.W., A.L.F., A.J.F.), University of Cambridge, Cambridge CB2 3EG, United Kingdom; Department of Medicine (S.L.K.), University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Department of Obstetrics and Gynaecology (G.C.S.S., D.S.C.-J.), University of Cambridge, The Rosie Hospital, Cambridge CB2 0SW, United Kingdom; School of Animal Biology (D.B.), University of Western Australia, Crawley, Perth, Western Australia, Australia 60095; and Department of Biological and Medical Sciences (A.J.F.), Oxford Brookes University, Oxford OX3 0BP, United Kingdom.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Hughes
authors.affiliation: Department of Physiology, Development and Neuroscience (M.J.D.B., M.B., A.D., A.H., F.B.P.W., A.L.F., A.J.F.), University of Cambridge, Cambridge CB2 3EG, United Kingdom; Department of Medicine (S.L.K.), University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Department of Obstetrics and Gynaecology (G.C.S.S., D.S.C.-J.), University of Cambridge, The Rosie Hospital, Cambridge CB2 0SW, United Kingdom; School of Animal Biology (D.B.), University of Western Australia, Crawley, Perth, Western Australia, Australia 60095; and Department of Biological and Medical Sciences (A.J.F.), Oxford Brookes University, Oxford OX3 0BP, United Kingdom.
authors.forename: F B Peter
authors.initials: FB
authors.lastname: Wooding
authors.affiliation: Department of Physiology, Development and Neuroscience (M.J.D.B., M.B., A.D., A.H., F.B.P.W., A.L.F., A.J.F.), University of Cambridge, Cambridge CB2 3EG, United Kingdom; Department of Medicine (S.L.K.), University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Department of Obstetrics and Gynaecology (G.C.S.S., D.S.C.-J.), University of Cambridge, The Rosie Hospital, Cambridge CB2 0SW, United Kingdom; School of Animal Biology (D.B.), University of Western Australia, Crawley, Perth, Western Australia, Australia 60095; and Department of Biological and Medical Sciences (A.J.F.), Oxford Brookes University, Oxford OX3 0BP, United Kingdom.
authors.forename: Dominique
authors.initials: D
authors.lastname: Blache
authors.affiliation: Department of Physiology, Development and Neuroscience (M.J.D.B., M.B., A.D., A.H., F.B.P.W., A.L.F., A.J.F.), University of Cambridge, Cambridge CB2 3EG, United Kingdom; Department of Medicine (S.L.K.), University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Department of Obstetrics and Gynaecology (G.C.S.S., D.S.C.-J.), University of Cambridge, The Rosie Hospital, Cambridge CB2 0SW, United Kingdom; School of Animal Biology (D.B.), University of Western Australia, Crawley, Perth, Western Australia, Australia 60095; and Department of Biological and Medical Sciences (A.J.F.), Oxford Brookes University, Oxford OX3 0BP, United Kingdom.
authors.forename: Abigail L
authors.initials: AL
authors.lastname: Fowden
authors.affiliation: Department of Physiology, Development and Neuroscience (M.J.D.B., M.B., A.D., A.H., F.B.P.W., A.L.F., A.J.F.), University of Cambridge, Cambridge CB2 3EG, United Kingdom; Department of Medicine (S.L.K.), University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Department of Obstetrics and Gynaecology (G.C.S.S., D.S.C.-J.), University of Cambridge, The Rosie Hospital, Cambridge CB2 0SW, United Kingdom; School of Animal Biology (D.B.), University of Western Australia, Crawley, Perth, Western Australia, Australia 60095; and Department of Biological and Medical Sciences (A.J.F.), Oxford Brookes University, Oxford OX3 0BP, United Kingdom.
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Forhead
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D046128:Fetal Therapies; D005333:Fetus / Q000187:drug effects*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007262:Infusions, Intravenous; D020738:Leptin / Q000008:administration & dosage / Q000235:genetics / Q000493:pharmacokinetics / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism / Q000502:physiology; D008170:Lung Compliance / Q000187:drug effects; D038081:Organogenesis / Q000187:drug effects*; D011247:Pregnancy; D037701:Pulmonary Surfactant-Associated Protein B / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D054411:Receptors, Leptin / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D012756:Sheep; D014109:Total Lung Capacity / Q000187:drug effects
chemical_list: D020738:Leptin; D037701:Pulmonary Surfactant-Associated Protein B; D012333:RNA, Messenger; D054411:Receptors, Leptin; D011994:Recombinant Proteins