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 subse quent bronchopulmonary dysplasia (BPD), due to deficit in pulmonary su rfactant; 2) neonatal supplementation with retinol reduces the risk of BPD; and 3) fetal rat lung stores retinol in late gestation just befo re the onset of surfactant synthesis. To test the hypothesis of an imp lication of retinoids in the control of pulmonary surfactant synthesis , experiments were designed in the pregnant rat, aiming either at enha ncing fetal lung vitamin A stores, bringing the active metabolite of v itamin 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 a nd 29%, respectively, the total phospholipid (TPL) and disaturated fra ction of phosphatidylcholine (PC) in extracted fetal surfactant on day 19 but did not change surfactant protein (SP) A concentration. Chroni c administration of retinyl palmitate to the mother from day 16 throug h 20 increased disaturated PC content on day 21 but decreased SP-A con centration. Fetal lung surfactant phospholipids were increased by chro nic administration of RA and considerably reduced by citral (-31 and - 35% for TPL and PC concns, respectively). RA also enhanced labeled cho line incorporation into fetal lung PC on day 20. Given once on day 17, it accelerated the appearance of surfactant precursors on day 18. In vitro, RA stimulated H-3-labeled acetate incorporation into phospholip ids and their precursors, 1,2-diglycerides, in isolated fetal lung typ e II cells, the surfactant-producing cells. We concluded that lung vit amin A stores play a role in the control of surfactant phospholipid on togeny in the developing lung and that RA is the active mediator of th is action.