Effect of extracellular myo-inositol on surfactant phospholipid synthesis in the fetal rabbit lung.
In the present investigation, myo-inositol was elevated in fetal serum by dietary manipulation. The myo-inositol-containing diet doubled the already high fetal serum myo-inositol between fetal days 26 and 28 but had no detectable effects on the lung. However, myo-inositol decreased betamethasone-induced (0.2 mg/kg, days 26.3 and 27.3, to the doe) inhibition in lung growth and potentiated the hormone-induced increase in alveolar space saturated phosphatidylcholine. This effect could not be explained by alteration of glucocorticoid-stimulated enzyme activity (phosphatidate cytidylyltransferase, phosphatidic acid phosphohydrolase, choline phosphate cytidylyltransferase) in the lung. Lung explants from 26-day-old fetuses were grown in a serum-free medium for 4 days. myo-Inositol (1.5 mM) had only a small effect on the phospholipid incorporation. Dexamethasone and thyroxine increased the incorporation of the precursors into surfactant phosphatidylglycerol and saturated phosphatidylcholine. myo-Inositol, in the presence of the hormones, switched the acidic surfactant phospholipid from phosphatidylglycerol to phosphatidylinositol and further increased the incorporation of surfactant-associated saturated phosphatidylcholine. myo-Inositol-excess preferentially increased the incorporation of NADPH (derived from glucose) and acetate into the fatty acid moiety of surfactant phosphatidylcholine. It is proposed that the high extracellular myo-inositol in immature fetuses provides an environment that promotes both the hormone-stimulated differentiation and the growth.
D000818:Animals; D001623:Betamethasone / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D005958:Glucosephosphates / Q000378:metabolism; D007294:Inositol / Q000494:pharmacology*; D008168:Lung / Q000196:embryology*; D009924:Organ Culture Techniques; D010743:Phospholipids / Q000096:biosynthesis; D011650:Pulmonary Alveoli / Q000201:enzymology / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000096:biosynthesis*; D011817:Rabbits
D005958:Glucosephosphates; D010743:Phospholipids; D011663:Pulmonary Surfactants; D007294:Inositol; D001623:Betamethasone