IN-VIVO LOCALIZATION OF THE INSULIN-LIKE GROWTH-FACTOR-I AND GROWTH-FACTOR-II (IGF-I AND IGF-II) GENE-EXPRESSION DURING HUMAN LUNG DEVELOPMENT

The insulin-like growth factors I and II (IGF I and IGF II) are synthe sized in many organs during human development and are involved in the growth and differentiation of tissues. Correlations between lung growt h and maturation and the local production of IGFs have been poorly exp lored in humans. Using in situ hybridization we localized the synthesi s of IGFs in the human fetal respiratory tract over an extended period of the gestation and we demonstrated time dependent changes. IGF mRNA s were expressed throughout gestation with a clear predominance of IGF II and a decreasing expression of both IGFs after the 20th week of ge station. They were mainly detected in the mesodermal-derived component s of the respiratory tract, especially in the undifferentiated mesench yme of the lung buds up to 20 weeks of gestation. At this time the loc al production of collagen and the proliferation of adjacent epithelial cells were predominant features. Later, mesenchymal hybridization dec reased. Weak epithelial hybridization was observed during the first st ages of growth and progressively decreased when the epithelium underwe nt maturation: early in the trachea, later in the distal lung buds. A consistent expression of IGF II, but not IGF I, in the endothelium, th roughout gestation, was also observed. The IGFs may act on the near ep ithelial cell proliferation in both autocrine and paracrine ways. They may also stimulate the maturation of the connective tissue. This endo genous production of growth factors may play a role in the somatic gro wth during prenatal life.