To assess effects of antenatal glucocorticoid treatment on surfactant components, we treated pregnant sheep using a clinically relevant, repeated dosing schedule. Sheep received 1-4 doses of betamethasone 0.5 mg/kg i.m. at 104 days gestation, 104+111 d, 104+111+118 d, or 104+111+118+124 d or saline(control) with delivery of all fetuses at 125 d. Lambs were ventilated for 40 min and both lung tissue and lavage were assayed for surfactant proteins A and B by immunoassay and for saturated phosphatidylcholine (Sat PC) by lipid extraction and chromatography. In addition, tissue was assayed for fatty acid synthetase (FAS, 14C-malate incorp. into FA) and cholinephosphate cytidylyltransferase (CYT, 14C-CDP choline formation). With increasing doses there was a progressive, parallel increase in content of SP-A, SP-B and Sat PC in both tissue and lavage with a maximal response after 3 doses.Table

Table 1

There was a close correlation between SP-A and SP-B in lavage (r=0.92) and lesser correlations between Sat PC and SP-A (r=0.65) and SP-B (r=0.60). FAS and CYT activities were not affected by treatment, suggesting glucocorticoid regulation of other steps in Sat PC synthesis. We conclude that repeated betamethasone treatment of sheep increases production and secretion of SP-A, SP-B and Sat PC in a coordinated fashion and that induction is partially reversible and/or gestational age dependent.