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The Influence of Hormones on the Biochemical Development of Fetal Rat Lung in Organ Culture. II. Insulin

Summary: The influence of insulin on the biochemical and morphologic maturation of 19-day fetal rat lung (term is 22 days) was studied in an organ culture system. Exposure to insulin for 24 hr resulted in a significant increase in the glycogen content and the rate of glucose oxidation to CO2. In association with this, there was morphologic evidence of delayed lung maturation as evidenced by a significant decrease in the number of lamellar bodies and type II cells in the explants.Insulin treatment had no effect on the rate of choline incorporation into phosphatidylcholine (PC) or disaturated PC and did not antagonize the dexamethasone-induced stimulation of choline incorporation into PC. When the incorporation of [3H]acetate into the various phospholipid fractions was examined, however, it was found that exposure to insulin resulted in a significant decrease in the percentage of phospholipid radioactivity in the disaturated PC fraction and an increase in the percentage of radioactivity in the “membrane” phospholipids, phosphatidylethanolamine, phosphatidylinositol plus phosphatidylserine, and sphingomyelin. There was no significant change in the unsaturated PC and phosphatidylglycerol fractions. Treatment with dexamethasone generally had the opposite effect to insulin with regard to acetate incorporation into the various phospholipid fractions, and when the two hormones were combined, this effect was diminished or abolished. The effects of insulin could not be accounted for on the basis of a change in activity of any of the enzymes of phospholipid synthesis that were examined.These findings suggest that insulin stimulates the synthesis of the cell membrane phospholipids while decreasing that of the surfactant phospholipid, disaturated PC.Speculation: Insulin stimulates lung cell growth while delaying lung cell differentiation.