DIFFERENTIAL REGULATION OF GLUCOCORTICOID RECEPTOR EXPRESSION BY LIGAND IN FETAL RAT LUNG-CELLS

The glucocorticoid receptor (GR) mediates glucocorticoid stimulation o f surfactant production by fetal mammalian lung. In many other tissues , glucocorticoids decrease expression of GR, thereby reducing responsi veness to these hormones. We therefore determined whether there is a s imilar effect of exogenous glucocorticoids on GR in fetal rat whole lu ng, and in the principal cell types involved in the stimulation of sur factant, the fibroblasts and the epithelial cells. The ontogeny of GR in late gestation lung differed between the two cell types, with maxim al levels occurring in fibroblasts on gestational d 19, and on d 20 in epithelial cells. Administration of dexamethasone (1 mg/kg) to the mo ther on gestational d 18 or 19 (term = 22 d) increased specific GR bin ding activity in whole lung 24 h later. Furthermore, in vitro, incubat ion of cultured fibroblasts of gestational d 20 with 10(-7) M cortisol increased GR immunoreactive protein and binding activity in a dose- a nd time-dependent manner, without affecting cellular levels of GR mRNA , However, identical treatment of d 20 distal airway epithelial cells was followed by decreased GR protein without significant change in cel lular GR mRNA. Surfactant protein-A protein levels, taken as assessmen ts of lung maturation, were increased in response to the same treatmen t. Our findings suggest that hormonal regulation of GR in fetal lung c ells occurs at a posttranscriptional level, and is cell-specific. In t he context of substantial increases in circulating glucocorticoid conc entrations during late gestation, these findings may be of physiologic importance to the biochemical maturation of the antenatal lung.