SPATIAL AND TEMPORAL DISTRIBUTION OF INSULIN-LIKE GROWTH FACTOR-I AND FACTOR-II DURING DEVELOPMENT OF RAT LUNG

Insulin-like growth factors (IGF) I and II genes are expressed in developing lung tissue, but tile details of distribution during different stages of lung development have not been delineated. To define the role of IGFs in lung development, the expression of IGF-I and IGF-II mRNAs and peptides was examined in rat lungs from 16-day gestation through adulthood. The expression of stable IGF mRNAs was investigated by Northern analysis, IGF mRNAs were localized by in situ hybridization histochemistry, and IGF peptides were localized by immunohistochemistry. Four IGF-II transcripts (3.5, 2.2, 1.8, and 1.0 kb) were identified; IGF-II mRNA levels were highest early in fetal life (day 16-18) and decreased gradually until 28 days postnatal. Four IGF-I transcripts (7.8, 4.4, 2.1, and 0.6 kb) were detected but were of low abundance. IGF-II mRNA was localized mainly in mesenchymal cells but was also identified in the airway epithelium, with peak expression in the perinatal lung. IGF-II peptide was prominent in late fetal life and for 5 days after birth and was identified in both mesenchymal and epithelial cells. In contrast, there was little evidence of IGF-I mRNA and peptide until after birth: IGF-I was most easily identified between 5 and 14 days postnatal (the height of alveolar multiplication and formation), when both mRNA and peptide were localized to mesenchymal and epithelial cells. Our studies demonstrate that IGF-I and IGF-II are synthesized and distributed in spatially and temporally different patterns in the developing lung. IGF-I and IGF-II peptides are more widely identified than their respective mRNAs, suggesting a paracrine distribution in the developing lung.