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

Abstract

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 5 4), at mid gestation (days 98 -102, n 5 4), and late in gestation (days 158 -165, n 5 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 6 1.1 ng/ml (mean 6 S.E.M.) in mid pregnancy and 8.4 6 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.

Loss of Phosphatase and Tensin Homolog (PTEN) Induces Leptin-mediated Leptin Gene Expression

“…Increased pulmonary and circulating LEP levels are observed with several lung diseases associated with injury/repair and remodeling, including lung cancer (5, 66 -68). LEP is also involved in fetal lung development and pulmonary homeostasis (69,70). Emerging evidence indicates that LEP as a pro-inflammatory and pro-angiogenic cytokine may play critical roles in exacerbating acute and chronic pulmonary pathologies and drive lung cancer as an inflammatory molecule (6,11,71).…”

CAATT/Enhancer-binding Proteins α and δ Interact with NKX2-1 to Synergistically Activate Mouse Secretoglobin 3A2 Gene Expression

“…These results suggest that the marked increase in C/EBP␦ in the bronchial epithelial cells may be largely responsible for the marked increase in expression of SCGB3A2 in these cells toward the end of gestation. Several genes are known to display increased expression toward the end of gestation such as SP-A, -B, and -D (43,44), aquaporin 1 (45), leptin receptor (46), and SCGB1A1 (10,19). SCGB3A2 may be added to the list of genes that increase their expression toward the end of gestation.…”

Postnatal leptin is necessary for maturation of numerous organs in newborn rats

“…This result contrasts with several studies carried out during fetal life, demonstrating an important role for leptin in the lung development of different species, such as rodents or primates. 29,30 At that stage, leptin receptors have been identified in the pneumocyte type II cells, which are responsible for synthesizing pulmonary surfactant and are developmentally regulated during late phases of gestation. 29,30 The lack of efficacy of leptin blockage during our study may suggest that its action on lung maturity is probably restricted to the gestational period in normal animals.…”