Glucocorticoid receptor mRNA and protein in fetal rat lung in vivo: modulation by glucocorticoid and androgen

Abstract

Pulmonary glucocorticoid receptor (GR) is essential to timely preparation for the onset of breathing air at birth. We have previously used primary culture of late-gestation fetal rat lung cells to demonstrate differential regulation of GR by glucocorticoid depending on cell type. In this study, we hypothesized that the action of glucocorticoid on GR mRNA expression and protein elaboration in lung cells might be modulated by interactions present in vivo but not in primary culture. Given that male sex hormone (androgen) has an inhibitory effect on antenatal lung development, we also postulated that androgen would decrease antenatal lung GR. We report that antenatal maternal injection of the glucocorticoid dexamethasone (1 mg/kg) enhanced fetal lung cellular levels of GR mRNA and protein as assessed by in situ hybridization and immunocytochemistry (ICC), respectively. ICC was performed using polyclonal rabbit anti-human antibody that reacts with rat GR whether bound to ligand or not and does not interfere with GR binding to DNA. Levels of GR mRNA and protein were enhanced in cells throughout all areas of the lung tissue, suggesting that interactions occurring in intact tissue may override the previously reported direct inhibition by glucocorticoid of GR protein elaboration in isolated fetal rat lung epithelial cells. Furthermore, antenatal administration of the androgen 5α-dihydrotestosterone (0.2 mg/kg) reduced tissue levels of GR mRNA and protein, consistent with androgenic inhibition of antenatal lung development by decreasing GR. We conclude that glucocorticoids and androgens exert opposite effects on fetal lung GR.

Postnatal glucocorticoids induce α-ENaC formation and regulate glucocorticoid receptors in the preterm rabbit lung

“…These in vivo findings (Figs. 8. and 9) support previously described studies in fetal and adult rat lung demonstrating that exogenous GC can either up-or downregulate the level of their own receptor by a variety of mechanistic pathways including transcriptional, posttranscriptional, and translational (28,29,49).…”

“…One particular gene regulated by GC is the GCR gene itself (17,28,29,49). A change in the expression of basal levels of GCR in either whole tissue or isolated cell culture by exogenous GC is described as autoregulation (28)(29)(30)49). In these particular studies we observed that treatment of 29-day GA preterm rabbits with Dex for 8 h did not greatly alter whole lung GCR mRNA expression.…”

“…GC play a major role during embryonic lung development and maturation (8,14,15,17,21,23,49). The physiological effects of GC are mediated by intracellular GCR that function as ligand-dependent transcription factors (8,14,17,49).…”

“…The physiological effects of GC are mediated by intracellular GCR that function as ligand-dependent transcription factors (8,14,17,49). Cellular GCR levels are thought to be a limiting factor in the signal transduction pathway, resulting in transcriptional responses to GC (17,(28)(29)(30)42).…”

“…In the lung, GC bound to its intracellular receptor acts in a manner that alters the rate of transcription of specific genes (17). One particular gene regulated by GC is the GCR gene itself (17,28,29,49). A change in the expression of basal levels of GCR in either whole tissue or isolated cell culture by exogenous GC is described as autoregulation (28)(29)(30)49).…”