Retinoids control surfactant phospholipid biosynthesis in fetal rat lung.
Vitamin A (retinol) may play an important role in lung maturation: 1) premature delivery is simultaneously a source of vitamin A deficiency and increased risk of neonatal respiratory distress syndrome and subsequent bronchopulmonary dysplasia (BPD), due to deficit in pulmonary surfactant; 2) neonatal supplementation with retinol reduces the risk of BPD; and 3) fetal rat lung stores retinol in late gestation just before the onset of surfactant synthesis. To test the hypothesis of an implication of retinoids in the control of pulmonary surfactant synthesis, experiments were designed in the pregnant rat, aiming either at enhancing fetal lung vitamin A stores, bringing the active metabolite of vitamin A, retinoic acid (RA), or inhibiting the conversion of retinol to RA with aid of citral. Maternal administration of a single dose of 50,000 IU of retinyl palmitate on day 16 (term 22 days) increased 22 and 29%, respectively, the total phospholipid (TPL) and disaturated fraction of phosphatidylcholine (PC) in extracted fetal surfactant on day 19 but did not change surfactant protein (SP) A concentration. Chronic administration of retinyl palmitate to the mother from day 16 through 20 increased disaturated PC content on day 21 but decreased SP-A concentration. Fetal lung surfactant phospholipids were increased by chronic administration of RA and considerably reduced by citral (-31 and -35% for TPL and PC concns, respectively). RA also enhanced labeled choline incorporation into fetal lung PC on day 20. Given once on day 17, it accelerated the appearance of surfactant precursors on day 18.(ABSTRACT TRUNCATED AT 250 WORDS)
Institut National de la Santé et de la Recherche Médicale U 319, Unité de Développement Normal et Pathologique des Fonctions Epithéliales, Université Paris 7, France.
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Fraslon
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JR
Bourbon
D000085:Acetates / Q000378:metabolism; D000080462:Acyclic Monoterpenes; D000818:Animals; D002478:Cells, Cultured; D002794:Choline / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000166:cytology / Q000378:metabolism*; D050356:Lipid Metabolism; D008168:Lung / Q000196:embryology* / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D039821:Monoterpenes; D010713:Phosphatidylcholines / Q000378:metabolism; D010743:Phospholipids / Q000096:biosynthesis*; D011247:Pregnancy; D011663:Pulmonary Surfactants / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D012176:Retinoids / Q000494:pharmacology*; D013729:Terpenes / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D014801:Vitamin A / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology
D000085:Acetates; D000080462:Acyclic Monoterpenes; D039821:Monoterpenes; D010713:Phosphatidylcholines; D010743:Phospholipids; D011663:Pulmonary Surfactants; D012176:Retinoids; D013729:Terpenes; D014801:Vitamin A; D014212:Tretinoin; D002794:Choline; C007076:citral