REGULATION OF SURFACTANT PROTEIN-D EXPRESSION BY GLUCOCORTICOIDS IN-VITRO AND IN-VIVO

SP-D is a recently described lung-associated protein that is produced by alveolar type II cells and may function in pulmonary host defenses. Since little is known regarding the hormonal regulation of SP-D, and since the other surfactant proteins (SP-A, SP-B, and SP-C) am known to be regulated by glucocorticoids, we sought to determine the effects o f glucocorticoids on SP-D mRNA and protein expression, both in vitro a nd in vivo, in the fetal rat lung. In vitro experiments were performed on lung explants from fetuses on gestational day 15 or 18. Explants w ere cultured in serum-free conditions with or without hydrocortisone f or 3 days. SP-D mRNA expression was evaluated by Northern blot analysi s. SP-D protein expression was analyzed using a polyclonal antibody ag ainst SP-D and standard immunohistochemical techniques. The expression of SP-D mRNA increased in fetal day 15 explants but remained unchange d in fetal day 18 explants cultured without the addition of hydrocorti sone, compared with in vivo controls. The addition of hydrocortisone r esulted in increases in SP-D mRNA expression at both gestational ages. This pattern of SP-D mRNA expression was compared with the expression of the other surfactant proteins and found to be most similar to that of SP-B. In vivo experiments were performed using maternal administra tion of dexamethasone (1 mg/kg) or an equal volume of saline on fetal days 15, 16, and 17 or on fetal day 17 with sacrifice on fetal day 18. Precocious expression of SP-D mRNA and protein was seen in vivo with maternal administration of dexamethasone. These findings demonstrate t hat SP-D is regulated by glucocorticoids both in vitro and in vivo and suggest that SP-D is differentially regulated from the other surfacta nt proteins.