Previous studies have shown that triiodothyronine (T3) enhances the effect of dexamethasone on phosphatidylcholine (PC) synthesis in organ cultures of fetal rat lung. The aim of this study was to investigate whether similar interactions occurred in vivo and to explore possible mechanisms for this phenomenon. Injection of 7.0 mg/kg T3 into pregnant rats on d 18 and 19 of gestation resulted in a mean fetal serum T3 level of 2380 ng/dl on d 20 (control, 84 ng/dl) and in maximal (34%) stimulation of choline incorporation into PC. Injection of 1.0 mg/kg betamethasone using the same protocol as for T3 resulted in maximal stimulation of 33% and administration of both hormones together produced a 69% increase, an additive affect. The percentage of PC that was disaturated was increased with betamethasone, but decreased with T3. Betamethasone treatment resulted in an increase in the whole lung disaturated PC content, but treatment with T3 did not. Betamethasone administration also increased fetal serum T3 levels, but T3 injection did not produce elevated fetal serum corticosterone levels. Injection of T3 in vivo, or exposure of explants of 18-d fetal lung to 100 nm T3 for up to 48 h did not result in an increase in cytoplasmic glucocorticoid binding or nuclear translocation of the receptor steroid complex. Exposure of explants to glucocorticoid or T3 in vivo or in culture (dexamethasone, 100 nM and T3, 100 nM; for 48 h) resulted in a significant increase in the activity of cholinephosphate cytidylyltransferase, an enzyme in the choline incorporation pathway of PC synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

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Summary ated species of this phospholipid is believed to play a major role In lowering surface tension at the air-alveolar interface, thereby PC in the lungs of the fetuses of glucose-intolerant monkeys. InInsulin treatment had no effect on the rate of choline incorpoaddition, Moxley and L~~~~~~~ found ,hat glucose ration into phosphatidylcholine (PC) or disaturated PC and did into PC in isolated, perfused rat lungs was decreased not antagonize the dexamethasone-induced stimulation of choline when the lungs of adult diabetic rats were used. These effects incorporation into PC. When the incorporation of IVilacetate into be reversed by insulin treatment prior to perfusion. the various phospholipid fractions was examined, however, i t was of insulin action. which depend on isotope incorporation into found that exposure to insulin resulted i n a significant decrease i n phospholipids. are, however. complicated by t h e fact insulin the percentage of phospholipid radioactivity in the disaturated PC [he uptake of some substrates into cells and may also fraction and an increase i n the percentage of radioactivity i n the influence the intracellular pool size of these substrates, had the nppnsite effect to insulin with regard to acetate incorpo-phol,p,ds other than PC. was ~h~~~ included the imration into the various phospholipid fractions, and when the two portant surfactant components disaturated PC and phosphatidylhormones were combined, this effect was diminished or abolished. glycerol ( 19. I ) as well as the phosphol,p,dh usually The effects of insulin could not be accounted for on the basis of a with cell membranes. mono-and unsaturated PC.. phosphatidylchange i n activity of any of the enzymes of phospholipid synthesis elhanolamine, phosphat,dylinositol. phosphatidylserine. and that were examined. sphingomyelin (27). The influence of insulin on enzymes involvedThese findings suggest that insulin stimulates the synthesis of with pulmonary phospholipid synthesis was also examined, the cell membrane phospholipids while decreasing that of the surfactant phospholipid, disaturated PC.