GLUCOCORTICOID REGULATION OF SURFACTANT COMPONENTS IN IMMATURE LAMBS

To assess effects of dose and duration of glucocorticoid exposure on m aturation of the fetal lung, we administered single or multiple doses of betamethasone (0.5 mg/kg im) to pregnant sheep for 2 or 21 days bef ore preterm delivery at 125 days of gestation. Lung function (complian ce, lung volume at 40 cmH(2)O pressure, and ventilatory efficiency ind ex) was increased after two to four weekly doses of glucocorticoid (2. 5- to 4-fold increase) and after 48 h of exposure (1.4- to 2.3-fold). Total protein of lavage fluid decreased similarly with three doses, fo ur doses, and 48 h of treatment. In lambs with long-term exposure to b etamethasone, there was a similar, dose-dependent increase in concentr ations of saturated phosphatidylcholine and surfactant proteins A (SP- A) and B (SP-B) (maximal 2- to 3-fold in tissue and 10- to 15-fold in lavage fluid). Levels of SP-A and SP-B were closely correlated in lava ge fluid. In animals treated for 48 h, only tissue SP-B was increased (2.7-fold). We conclude that 48 h of glucocorticoid treatment improves lung function in the premature lamb without a detectable increase in lavage surfactant components and that longer exposure to antenatal glu cocorticoid increases surfactant lipid and proteins in a coordinated f ashion. The enhanced response with repetitive dosing indicates that th e process of glucocorticoid-induced lung maturation is either reversib le and/or gestational age dependent.