Developmental and Glucocorticoid Regulation of Surfactant Protein mRNAs in Fetal Sheep † 310

We previously found that glucocorticoid treatment of pregnant sheep increases the content of surfactant proteins SP-A and SP-B in lung tissue and lavage of preterm lambs. To investigate the mechanism of this induction process, we quantitated SP mRNA levels after administration of betamethasone(0.5 mg/kg) to pregnant sheep prior to premature delivery of the fetus at 125 days. In the first protocol, 55 sheep were injected weekly with 1-4 doses of either saline (control) or betamethasone beginning at 104 days gestation with the last dose given 24 h prior to delivery. In a second protocol, 39 sheep were injected with 1-2 doses of saline or betamethasone at 24 and 48 h prior to delivery. Total RNA was extracted from fetal lung and hybridized with cDNAs for sheep SP-A, SP-B and SP-C and human β-actin. mRNA levels for control preterm lambs were 21%, 28% and 39% of the level in term lambs for SP-A, -B and -C, respectively. No increases in mRNA levels were demonstrated in sheep given 1-3 weekly doses of betamethasone vs. control. However, 4 doses of betamethasone, as well as both 48h treatment regimens, produced a 2- to 3-fold increase in each SP mRNA (p