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 synthesized in many organs during human development and are involved in the growth and differentiation of tissues. Correlations between lung growth and maturation and the local production of IGFs have been poorly explored in humans. Using in situ hybridization we localized the synthesis of IGFs in the human fetal respiratory tract over an extended period of the gestation and we demonstrated time dependent changes. IGF mRNAs were expressed throughout gestation with a clear predominance of IGF II and a decreasing expression of both IGFs after the 20th week of gestation. They were mainly detected in the mesodermal-derived components of the respiratory tract, especially in the undifferentiated mesenchyme of the lung buds up to 20 weeks of gestation. At this time the local production of collagen and the proliferation of adjacent epithelial cells were predominant features. Later, mesenchymal hybridization decreased. Weak epithelial hybridization was observed during the first stages of growth and progressively decreased when the epithelium underwent maturation: early in the trachea, later in the distal lung buds. A consistent expression of IGF II, but not IGF I, in the endothelium, throughout gestation, was also observed. The IGFs may act on the near epithelial cell proliferation in both autocrine and paracrine ways. They may also stimulate the maturation of the connective tissue. This endogenous production of growth factors may play a role in the somatic growth during prenatal life.