AJP - Lung Cellular and Molecular Physiology, Vol 266, Issue 6 705-L712, Copyright © 1994 by American Physiological Society
Retinoids control surfactant phospholipid biosynthesis in fetal rat lung
C. Fraslon and J. R. Bourbon
Institut National de la Sante et de la Recherche Medicale U 319, Unite de Developpement Normal et Pathologique des Fonctions Epitheliales, Universite Paris 7, France.
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)
