Though clinical trials with maternal corticosteroids (CS) plus Thyrotropin Releasing Hormone (TRH) for prevention of Hyaline Membrane Disease (HMD) of the premature neonate are ongoing, the effect of maternal CS+TRH therapy on the developmental expression of fetal lung SP-A, SP-B or SP-C protein or mRNA has not been investigated. Saline, Betamethasone (Beta., Celestone, 0.1 ml/dose), TRH (0.4 mg/kg/dose) or Beta.+TRH were injected (I.P., b.i.d.) into the pregnant Balb-c mouse on day 16 and 17 of gestation (vaginal plug=1 d of pregnancy, term ≈20 d). All mice were killed on d 18 of gestation and fetal lungs were saved for electron microscopy, immunostaining and Northern blot analysis for SP-A, SP-B and SP-C. Immunostaining was performed by using appropriate antibodies. The intensity and distribution of the immunoreactivity was scored on a scale of 0 to 3 in 0.5 increments. The staining for SP-A, SP-B and SP-C was cytoplasmic and present in type II cells as well as within the alveolar lumen. All data are means. Table
Conclusions: Overall fetal lung immunoreactivity for SP-A, SP-B and SP-C was increased in Beta. but not mice treated with TRH when compared to controls. No additive effect of Beta.+TRH over Beta. alone was observed. We speculate that the beneficial effect of prenatal CS+TRH therapy in the prevention of HMD in the human neonates is not due to an additive effect of TRH+CS on fetal lung surfactant protein expression.(NIH-HL-52839).
