EFFECTS OF MATERNAL DEXAMETHASONE ON EXPRESSION OF SP-A, SP-B, AND SP-C IN THE FETAL-RAT LUNG

Prenatal administration of glucocorticoids has been shown to enhance surfactant production in the fetus. Since the surfactant proteins play an important role in surfactant function and secretion, we wished to determine the effects of maternal glucocorticoid administration on their fetal expression and appearance. Daily dexamethasone (DEX) (1 mg/kg/day) or 0.9% saline was administered to timed-pregnant rats on gestational days 14 through 16 or on day 16 with sacrifice on day 17 (term day 22), and on gestational days 14 through 18, or days 16 through 18, or day 18 with sacrifice on day 19. SP-A content was determined in lung homogenates from treated and control male and female fetal rats by an enzyme-linked immunosorbent assay. The abundance of mRNAs for SP-A, SP-B, and SP-C per fixed amount of total cellular RNA was also determined in lungs from treated and control male and female fetal rats by Northern blot analysis. In litters sacrificed on day 17, DEX administered on days 14 through 16 and on day 16 resulted in significant increases in SP-A content. Expression of SP-A mRNA, which was not detectable in control fetuses on day 17, became clearly apparent after either 1 or 3 d of DEX treatment. The abundance of mRNAs for SP-B and SP-C also increased in day-17 fetuses after either 1 or 3 d of DEX treatment. In litters sacrificed on day 19, DEX administered on days 14 through 18 and on days 16 through 18 resulted in significant increases in SP-A content; treatment with DEX on day 18 had no effect on SP-A content. Interestingly, the abundance of SP-A mRNA did not change significantly in day-19 fetal lungs regardless of the duration of DEX treatment. The abundance of mRNAs for SP-B and SP-C, however, significantly increased in day-19 fetal lungs after 3 or 5 d of prior DEX treatment. Fetal sex had no effect on SP-A content and abundance of mRNAs for SP-A, SP-B, and SP-C in DEX-treated or control animals on either day 17 or 19. These findings suggest that maternal DEX treatment has different effects on SP-A and SP-A mRNA accumulation, depending on the stage of fetal lung development and duration of treatment. The effects of maternal DEX on mRNAs for SP-B and SP-C, however, appear to be independent of the stage of fetal lung development and duration of treatment, suggesting differential regulation of the surfactant protein genes in the developing rat lung.