Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0231807 (exertional dyspnea)
 3,402 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Effect of extracellular myo-inositol on surfactant phospholipid synthesis in the fetal rabbit lung. 654 57

In the present study we investigated the maturation of the surfactant phospholipids and the role of fetal sex on the effect of betamethasone in male and female rabbit fetuses. Betamethasone was administered to the doe (0.2 mg/kg intramuscularly) 42 and 18 h prior to killing. The fetuses were studied at 27 and 28 days from conception. Results from the alveolar lavage show that male fetuses tended to have a lower disaturated phosphatidylcholine/sphingomyelin ratio and lower levels of phosphatidylinositol. Phosphatidylglycerol was detected in trace amounts. This was apparently due to the high extracellular levels of myo-inositol inhibiting the synthesis of surfactant phosphatidylglycerol while increasing the synthesis of surfactant phosphatidylinositol. Betamethasone increased the recovery of disaturated phosphatidylcholine and phosphatidylinositol from the lung lavage in both sexes. As studied in lung slices in vitro, the betamethasone treatment decreased the incorporation of glucose into phospholipids, including into the fatty acid moiety of disaturated phosphatidylcholine, although it had no significant effect on the incorporation of glucose into the glycerol moiety of disaturated phosphatidylcholine. However, the addition of palmitate increased the incorporation of glucose into the glycerol moiety of disaturated phosphatidylcholine. The betamethasone treatment did not increase the incorporation of [1-14C]pyruvate into disaturated phosphatidylcholine. Following betamethasone administration, the availability of fatty acids may become rate-limiting for the synthesis of surfactant phospholipids. Betamethasone increased the activities of phosphatidic acid phosphohydrolase and phosphatidate cytidyltransferase in a fraction of microsomal membranes. The present evidence suggests that the glucocorticoid-induced lung maturation and the maturation of the normal lung are associated with an increase in the activity of the enzymes which are involved in metabolizing phosphatidic acid to neutral and acidic surfactant secretion of the male fetus was not explained by possible sex-related differences in the biosynthesis of the phospholipids.
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PMID:The effect of betamethasone and fetal sex on the synthesis and maturation of lung surfactant phospholipids in rabbits. 682 16