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Leptin receptor expression in fetal lung increases in late gestation in the baboon: a model for human pregnancy

Departments of ¹ Obstetrics and Gynecology, ² Physiology, ³ Structural and Cellular Biology and ⁴ Medicine, ⁵ Interdisciplinary Program in Molecular and Cellular Biology and ⁶ Tulane National Primate Research Center, Tulane University Health Sciences Center, New Orleans, Louisiana 70112, USA and ⁷ Department of Obstetrics and Gynecology, Texas Tech University Health Sciences Center, Amarillo, Texas 79106, USA

Correspondence should be addressed to M C Henson, Department of Obstetrics and Gynecology (SL-11), Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, Louisiana 70112-2699, USA; Email: henson{at}tulane.edu

Leptin produced by both adipose tissue and the placental trophoblast, has been proposed to regulate numerous aspects of human conceptus development. Although recent animal studies have suggested an additional role for the polypeptide in fetal lung maturation, no evidence has been reported in primates. Therefore, we employed the baboon (Papio sp.), a well-characterized primate model for human pregnancy, to determine the presence and ontogeny of leptin receptor in fetal lung with advancing gestation. Lungs were collected from fetal baboons, early in gestation (days 58–62, n = 4), at mid gestation (days 98–102, n = 4), and late in gestation (days 158–165, n = 4) (term 184 days). mRNA transcripts for leptin (LEP) and both long and short intracellular domain isoforms of the leptin receptor (LEP-R_L and LEP-R_S) were assessed by RT-PCR. leptin receptor protein was evaluated by immunoblotting and cell types expressing leptin receptor were identified in late pregnancy by immunohistochemistry. Fetal serum leptin concentrations, determined by RIA, remained relatively unchanged at 5.7 ± 1.1 ng/ml (mean ± S.E.M.) in mid pregnancy and 8.4 ± 3.0 ng/ml in late pregnancy (P > 0.05). Although leptin were detectable in fetal lung, no changes in transcript abundance were apparent with advancing gestation. However, transcripts for both LEP-R_L and LEP-R_S receptor isoforms increased several-fold (P < 0.05) in fetal lung between mid and late gestation, while leptin receptor protein was detectable only in late pregnancy. leptin receptor was localized in distal pulmonary epithelial cells, including type II pneumocytes. In conclusion, leptin is present in the fetal baboon and its receptor is enhanced during late gestation in cells responsible for the synthesis of pulmonary surfactant. Collectively, these and past findings may suggest a modulatory role for the polypeptide in pulmonary development and/or may identify leptin receptor as a physiological marker of primate fetal lung maturity.

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