Effects of epidermal growth factor (EGF) on the development of EGF-receptor (EGF-R) binding in fetal rabbit lung organ culture

Epidermal growth factor (EGF) causes gender- and development-specific chang es in fetal lung surfactant synthesis. We hypothesized that the effects of EGF on development of surfactant synthesis are related to effects on EGF re ceptor (EGF-R) expression. We prepared sex-specific fetal rabbit lung organ cultures on gestational days 21 and 24 (term = 31 days) in Waymouth's medi um + 10% charcoal-stripped fetal calf serum as control or with added EGF (1 0 ng/mL). After 3, 5, and 7 days of culture, we measured specific EGF-R bin ding in fetal lung plasma membrane preparations. Analysis of variance (ANOVA) revealed significant effects of fetal gender ( P = 0.0003), time in culture (P = 0.01), and EGF treatment (P = 0.0003) on EGF specific binding. In control cultures from days 21 and 24 (both male an d female), EGF specific binding tended to decrease with time in culture. Sp ecific binding in EGF-treated female 21-day cultures was significantly high er than in controls, both after 5 days (184% of control, P = 0.007) and aft er 7 days (151% of control, P = 0.01; Bonferroni multiple comparisons) of t reatment, whereas males exhibited no response to EGF treatment. As opposed to these effects in 21-day cultures, EGF had little effect on 24-day cultur es. We conclude that EGF affects the expression of the EGF-R on EGF specifi c binding in the fetal lung. The development of surfactant synthesis in the fetal lung may be controlled by upregulation of the EGF-R. (C) 2000 Wiley- Liss, Inc.