Fetal lung in organ culture. IV. Supra-additive hormone interactions

Corticosteroids, thyroid hormones, and theophylline have previously been shown to accelerate fetal lung maturation. We have examined the interactions between these agents in relation to phospholipid synthesis in explants of 18-day fetal rat lung in organ culture. Maximal stimulation of the rate of incorporation of choline into phosphatidylcholine, the most abundant phospholipid in pulmonary surfactant, was observed at a dexamethasone concentration of 100 nM. Exposure to 100 nM dexamethasone, 1.0 mM theophylline, or a combination of the two agents for 48 h resulted, respectively, in 144, 157, and 508% stimulation of the rate of incorporation of choline into disaturated phosphatidylcholine. Similar supra-additive interactions between dexamethasone and dibutyryl adenosine 3′,5′-cyclic monophosphate (cAMP) were observed, but the effects with caffeine were less striking. The increase in the rate of precursor incorporation was associated with a significant increase in the disaturated phosphatidylcholine content of the cultures. Combination of dexamethasone with 100 nM triiodothyronine (the concn producing maximal effects) also resulted in supra-additive stimulation but to a smaller degree. These findings of interactions in vitro suggest that the agents act on the lung at different biochemical sites, but the mechanisms whereby they interact at the cellular level have yet to be established. The data provide a rationale for in vivo animal studies of the effects of combined hormone administration on fetal lung maturation.