Effect of metopirone on the synthesis of lung surfactant in does and fetal rabbits.

Abstract

The possible role of endogenous corticosteroids in the induction of synthesis of lung surfactant in both maternal and fetal rabbits was investigated. Metopirone (SU 4885), which specifically inhibits B hydroxylation in the adrenal gland, thus preventing endogenous cortisol production was used in this study. Pregnant rabbits received one of four treatment regimens: saline, metopirone, cortisone or metopirone plus steroid for 6 days before delivery. Studies of the lungs of the adult rabbits revealed that lung weights and percent dry weight were not influenced by drug injection. However, lung DNA content (mg/g) in the metopirone-treated group was higher than the control group, indicating an increase in cell number. Compared to the saline-treated group there was a significant decrease in lung phospholipid content in the other three groups (p smaller than 0.005). A decrease in lung lecithin and phosphatidylethanolamine was also noted in these three groups indicating that the inhibition was in the early steps of biosynthesis of lung lecithin. The specific activity of 14C-labelled palmitate in lung lecithin was not altered by drug treatment indicating that saturated fatty acid incorporation into lung lecithin is not influenced by metopirone, steroid or a combination of both drugs. Quasi-static deflation pressure-volume characteristics of the lung were also similar in all groups. However, lungs of animals receiving both metopirone and steroid had a small but statistically significant decrease in minimum surface tension (p smaller than 0.05). The change in surface tension did not correlate with a change in lung retractive forces or with lung lipid content and was, therefore, of dubious biological significance. Metopirone administration to pregnant rabbits did not alter surface active properties in the fetus from the 26th to the 29th day of gestation when compared to control fetuses. At day 30-31 gestation the offsprings of metopirone-treated rabbits had lung total phospholipid and lecithin contents, and deflation pressure-volume curves similar to control group, but minimum surface tension of minced lung extracts were high in about 60% of the fetal lungs studied (p smaller than 0.05). These results suggest that endogenous steroid production may play a significant role in the maturation of the fetal lung.