Differential regulation of glucocorticoid receptor expression by ligand in fetal rat lung cells.
The glucocorticoid receptor (GR) mediates glucocorticoid stimulation of surfactant production by fetal mammalian lung. In many other tissues, glucorticoids decrease expression of GR, thereby reducing responsiveness to these hormones. We therefore determined whether there is a similar effect of exogenous glucocorticoids on GR in fetal rat whole lung, and in the principal cell types involved in the stimulation of surfactant, the fibroblasts and the epithelial cells. The ontogeny of GR in late gestation lung differed between the two cell types, with maximal levels occurring in fibroblasts on gestational d 19, and on d 20 in epithelial cells. Administration of dexamethasone (1 mg/kg) to the mother on gestational d 18 or 19 (term = 22 d) increased specific GR binding activity in whole lung 24 h later. Furthermore, in vitro, incubation of cultured fibroblasts of gestational d 20 with 10(-7) M cortisol increased GR immunoreactive protein and binding activity in a dose- and 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 cellular GR mRNA. Surfactant protein-A protein levels, taken as assessments of lung maturation, were increased in response to the same treatment. Our findings suggest that hormonal regulation of GR in fetal lung cells occurs at a posttranscriptional level, and is cell-specific. In the context of substantial increases in circulating glucocorticoid concentrations during late gestation, these findings may be of physiologic importance to the biochemical maturation of the antenatal lung.
Sweezey
N
N
Hospital for Sick Children Research Institute, University of Toronto, Ontario, Canada.
Mawdsley
C
C
Ghibu
F
F
Song
L
L
Buch
S
S
Moore
A
A
Antakly
T
T
Post
M
M
D000818:Animals; D002478:Cells, Cultured; D005333:Fetus / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006854:Hydrocortisone / Q000494:pharmacology; D008024:Ligands; D008168:Lung / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism
D008024:Ligands; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D006854:Hydrocortisone