REGULATION OF THE EPIDERMAL GROWTH-FACTOR RECEPTOR IN FETAL-RAT LUNG FIBROBLASTS DURING LATE-GESTATION

Lung epithelial cell differentiation is predominantly regulated by mes enchymal-epithelial cell communication. We have previously shown that epidermal growth factor (EGF) positively influences this process, and that EGF receptor (EGF-R) binding in fetal rat lung fibroblasts peaks on d18-19 of gestation, just before the onset of augmented surfactant synthesis. This regulation of EGF-R in late gestation fetal lung fibro blasts may control the timing of mesenchymal-epithelial cell communica tion leading to surfactant synthesis. Hormones and growth factors exer t positive and negative influences on luni: development, but whether t hey regulate the EGF-R is unknown. We hypothesized that positive [EGF, cortisol, retinoic acid (RA)] and negative [transforming growth-facto r-beta 1 (TGF-beta 1), dihydrotestosterone (DHT)] regulators of lung c ell development regulate the EGF-R in the fetal lung. We studied EGF-R binding and protein abundance in sex-specific fetal rat lung fibrobla sts cultured at d17, d19, and d21. EGF-R binding was significantly ele vated after RA (both sexes d17 and d19, females d21) and after DHT (fe males d19) treatment. EGF and cortisol had minimal or inhibitory effec ts on EGF-R binding. Western blot analysis showed that the observed ch anges in EGF-R binding were associated with similar changes in EGF-R p rotein. We conclude that factors that affect lung maturation continue to regulate EGF-R in a developmental, sex-specific manner during late gestation.