Somatomedin C/insulin-like growth factor I production by human fetal lung tissue maintained in vitro

The production of somatomedin C/insulin-like growth factor I (Sm-C/IGFI) by human fetal lung tissue maintained in vitro was examined in the present study. We have shown that epithelial cells in human fetal lung explants maintained in vitro differentiate into type II cells within 4-6 days. During the first 24 h of culture, the fetal lung explants released 2.74 +/- 0.14 ng Sm-C/IGFI/mg tissue protein into the culture medium. At this time the explants contained 0.24 +/- 0.02 ng Sm-C/IGFI/mg tissue protein. During the next 4 days of culture, explant Sm-C/IGFI content and the rate of Sm-C/IGFI secretion into the medium declined by approximately 50%. Sm-C/IGFI secretion was inhibited significantly when fetal lung explants were cultured in media that contained cortisol (10(-7) M), a hormone that is known to stimulate fetal lung type II cell differentiation. The effect of cortisol was both concentration- and time-dependent. While insulin, bovine prolactin, and human growth hormone had no apparent effect on Sm-C/IGFI production by the explants, human prolactin and human placental lactogen both decreased Sm-C/IGFI production. These findings are unprecedented and are suggestive that Sm-C/IGFI synthesis may be regulated in a unique fashion in the fetal lung. The decline in Sm-C/IGFI production by fetal lung tissue temporally correlates with the initiation of fetal lung type II cell differentiation in the human fetal lung explants.