DO EGF AND GLUCOCORTICOIDS ACT AT THE SAME METABOLIC SITES IN FETAL RAT LUNG?

Abstract

EGF enhances the morphological and physiological maturation of fetal lung in vivo and it has been suggested that it mediates T4 action on developing mouse skin. We examined the effects of EGF on the biochemical development of explants of 18 day fetal rat lung, maintained in a serum free organ culture system for 48h, in order to compare the effects of this peptide to those of T3 and dexamethasone (dex). EGF stimulated choline incorporation into phosphatidylcholine (PC) in a dose dependent fashion with half the maximal effect occurring at 1.0±0.1 nM (6 ng/ml). The effect of EGF on choline incorporation decreased with increasing gestational age whereas stimulation of thymidine incorporation into DNA increased, suggesting that EGF accelerates maturation of undifferentiated cells, but enhances multiplication of differentiated cells. EGF and dex significantly increased the distribution of radioactivity from acetate into the phosphatidylglycerol fraction, but T3 did not (PG as a % of total phospholipid: control, 1.8±0.2%; EGF, 4.4±0.4%; dex, 6.1±0.4%; T3, 2.0±0.4%). In mixing experiments using optimal concentrations, EGF (10 nM) produced 35% stimulation of choline incorporation; dex (100 nM), 47%; T3 (100 nM), 34%; EGF + T3, 75%; and EGF + dex, 43%. The fact that EGF + dex did not produce a greater effect than dex alone suggests that these 2 agents, but not T3, act at the same metabolic sites. We speculate that EGF may partially mediate the effects of dex on fetal lung maturation.