Lung-Derived Growth Factors: Ontogenic Shift in Parahormone Secretion in the Perinatal Rat Lung: (growth...

Primary cultures of perinatal rat fibroblasts were found to produce at least three mitogenic activities which exhibited specificity for distinct cell types. One activity, lung growth factor(LGF), was a potent mitogen for chick embryonal fibroblasts, which also stimulated fetal rat lung fibroblasts to undergo DNA synthesis, provided that these cells were first exposed to a "competence" factor such as fibroblast growth factor or platelet-derived growth factor. Although LGF was active in the somatomedin-C (SmC) radioimmunoassay and resembled buffalo rat liver multiplication-stimulating activity (brlMSA) in molecular size, it appears to consist of a component that is neither SmC nor brlMSA. The second activity produced by perinatal rat lung cultures, pneumocyte-stimulating activity (PSA), stimulated mitosis in type II pneumocytes of postnatal rats, and was found to have physical attributes that are distinct from those of the other known pneumocyte-influencing factors. The third activity is a non-dialyzable substance which complements the mitogenic action of LGF on fetal lung fibroblasts, and appears to be a "competence" activity. An examination of the production of LGF and PSA by rat lung fibroblasts taken at various intervals of development revealed that fetal lung fibroblasts produce maximal levels of LGF but low levels of PSA, whereas, in neonatal lung fibroblasts, the situation is reversed. This ontogenic shift in the type of parahormone produced by the developing perinatal rat lung may be an important regulatory event in postnatal lung morphogenesis in this species.