Effects of hydrocortisone and pilocarpine on fetal rat lung explants
Pysher, T.J.; Konrad, K.D.; Reed, G.B.
Laboratory Investigation; A Journal of Technical Methods and Pathology 37(6): 588-594
1977
ISSN/ISBN: 0023-6837 PMID: 579639 Document Number: 119330
An important phase of late gestational lung development is differentiation of alveolar epithelial cells into type II pneumocytes and subsequent elaboration by these cells of pulmonary surfactant. Hydrocortisone administration may accelerate both aspects of this process, whereas pilocarpine may facilitate the release of previously formed surfactant. Explants 1 mm3 of late gestational fetal rat lungs maintained in Medium 199 supplemented with 0.1% albumin, L-glutamine and glucose were used to study quantitatively the morphologic and biochemical effects of hydrocortisone and pilocarpine on synthesis and release of lecithin, the major lipid moiety of surfactant. Treatment for 24 h with 10-6 M hydrocortisone succinate apparently enhanced incorporation of 3H-choline and 14C-palmitic acid into lecithin in explants from fetuses of 19 days gestation (term = 21 days). This effect was not found in explants from fetuses of 15 or 17 days gestation or 8 day old newborn rats. Histologically, hydrocortisone-treated 19 day explants showed some increase in vacuolization of epithelial cells as compared to controls, and ultrastructurally there was a significant increase in epithelial cells containing osmiophilic inclusion bodies. No changes were seen in volume or cellular composition of the interstitium. There was no increase in overall rate of protein synthesis. Treatment of hydrocortisone-primed explants for 3 h with 10-6 M pilocarpine resulted in release of increased amounts of labeled lecithin and a concomitant increase in surface-active material in the culture media as determined by bubble stability tests. Enhancement of lecithin synthesis seen with hydrocortisone was an effect dependent upon gestational age and limited to the alveolar epithelial cell. Pilocarpine facilitated release of lecithin from explants.