AJP - Lung Cellular and Molecular Physiology, Vol 273, Issue 5 1048-L1057, Copyright © 1997 by American Physiological Society
Glucocorticoid regulation of surfactant components in immature lambs
P. L. Ballard, Y. Ning, D. Polk, M. Ikegami and A. H. Jobe
Department of Pediatrics, University of Pennsylvania School of Medicine, Children's Hospital of Philadelphia 19104, USA.
To assess effects of dose and duration of glucocorticoid exposure on
maturation 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 before
preterm delivery at 125 days of gestation. Lung function (compliance, lung
volume at 40 cmH2O pressure, and ventilatory efficiency index) 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, four doses, and 48 h of
treatment. In lambs with long-term exposure to betamethasone, there was a
similar, dose-dependent increase in concentrations 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 lavage 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 glucocorticoid increases surfactant lipid and
proteins in a coordinated fashion. The enhanced response with repetitive
dosing indicates that the process of glucocorticoid-induced lung maturation
is either reversible and/or gestational age dependent.
