ABSTRACT. Dexamethasone (Dex) and triiodothyronine (T3) were administered to pregnant rats during late gestation to evaluate potential developmental effects on fetal lung vitamin K-dependent carboxylation. Maternal rats were injected on the 2 d before study with Dex (0.2 mg/kg intraperitoneally), with T3 (0.7, 3.5, or 7 mg/kg intramuscularly), or with a combination of both hormones. Fetal lung microsomes were prepared at 18, 19, and 20 d of gestation, and carboxylase activity was assessed by measuring the incorporation of 14C02 into a synthetic pentapeptide substrate. Dex alone resulted in a small but consistent increase in activity in all three gestational ages. T3 alone increased activity approximately 85% at 20 d of gestation. Treatment with a combination of Dex and T3 caused a 60% increase in vitamin K-dependent carboxylation at each gestational age. Decreased lung growth was noted with combination hormone treatment in all rats studied at 19 and 20 d of gestation. Lung growth expressed as lung wt/ body wt was more sensitive to the effects of Dex plus T3 than was carboxylase activity. Decreased lung wt/body wt (decreased 25%) was noted with Dex plus T3 (0.7 mglkg); however, no induction of carboxylase enzyme activity was evident at this dose. This study demonstrates that vitamin K-dependent carboxylase activity in fetal rat lung can be induced by the exogenous administration of Dex and T3 to pregnant rats. Fetal lung microsomes contain multiple endogenous substrates for the vitamin K-dependent carboxylase enzyme. These hormones play a significant developmental role not only in protein biosynthesis, but in posttranslational processing as well. The more general effects of hormone treatment on lung growth can be distinguished from a relatively specific effect on lung vitamin Kdependent carboxylase activity by a difference in sensitivity of these responses to hormone treatment. (Pediatr Res 25: 530-534,1989) AbbreviationsPulmonary surfactant is a complex mixture of lipids, proteins, and carbohydrates that facilitates the maintainance of alveolar stability at low lung vol (1). Surface active characteristics of surfactant both in vivo and in vitro are dependent on complex interactions between the protein and lipid components (2). Surfactant proteins are specific to the lung and are subdivided into at least three groups: a higher rnol wt (28-40 kD) acidic group, and two lower mol wt lipophilic groups (2). The lower rnol wt proteins are intimately associated with the lipid components of surfactant and are required for their in vivo and in vitro activity (3, 4). The higher rnol wt proteins (SP-A), by contrast, further modify the surface characteristics of surfactant (3) and appear to be involved in the formation of the complex, three-dimensional, extracellular form of surfactant known as tubular myelin ( 5 ) . SP-A has also been implicated as having a regulatory role in surfactant lipid turnover (6) and may be involved in the immunologic defense of the alveolus (7).The interactions of SP-A with surfactant lipids a...