THE INSULIN-LIKE GROWTH-FACTORS AND THE LUNG

The insulin-like growth factors (IGF-I and IGF-II) are peptides of about 7,500 D with structural homology to proinsulin that are capable of stimulating cellular proliferation and inducing differentiation. They are each encoded by single, large, complex genes that direct the transcription of multiple mRNAs. Both genes are expressed in most organs and tissues, predominantly by cells of mesenchymal origin. Developmental factors are important in their regulation, with IGF-II's expression predominantly prenatally and IGF-I's postnatally. In the fetus, placental lactogen can stimulate the synthesis of both IGF-I and IGF-II. After birth, however, growth hormone and nutritional status are the major regulators of IGF-I. In addition, a variety of other factors exert tissue-specific stimulation of IGF-I and IGF-II expression. The actions of the IGFs are mediated by interaction with the type 1 IGF cell surface receptor, which, like the IGFs, is expressed in most tissues. The biologic effects of the IGFs are modulated by IGF binding proteins, which can both augment and inhibit IGF effects, depending on the nature of the binding protein and other factors. IGF actions are also influenced by other regulatory agents that appear to act in concert with the IGFs; for example, IGF-I's capacity to stimulate DNA synthesis in Balb-C 3T3 and FRTL5 cells requires other growth factors and TSH, respectively. The widespread expression of the IGFs, IGF receptors, and IGF binding proteins, taken together with the findings that the IGFs can act on many cell types, suggests that the IGFs have an important role in the growth and development of many organs, including lung.(ABSTRACT TRUNCATED AT 250 WORDS)