Glucocorticoid receptor mRNA and protein in fetal rat lung in vivo: modulation by glucocorticoid and androgen.
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 5alpha-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.
Sweezey
N B
NB
Respiratory Medicine, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
Ghibu
F
F
Gagnon
S
S
Schotman
E
E
Hamid
Q
Q
D000818:Animals; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D013196:Dihydrotestosterone / Q000494:pharmacology*; D005260:Female; D005333:Fetus; D005865:Gestational Age; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D008297:Male; D011247:Pregnancy; D014176:Protein Biosynthesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis*; D014158:Transcription, Genetic / Q000187:drug effects*
D005938:Glucocorticoids; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D013196:Dihydrotestosterone; D003907:Dexamethasone