Prenatal dexamethasone administration disrupts the pattern of cellular development in rat lung.
To examine whether prenatal exposure to glucocorticoids could adversely affect subsequent cellular development of the lung, we administered 0.2 mg/kg of dexamethasone to pregnant rats on gestational days 17, 18, and 19. Lungs of the offspring were then examined for patterns of cell acquisition (DNA) and growth (protein). DNA concentration (a marker of cell packing density) and DNA content (a measure of total cell numbers) were reduced during gestation, and the shortfalls in concentration persisted past weaning. Disruption of development was also apparent in the protein/DNA ratio, which was consistently elevated, a finding consistent with cellular hypertrophy. In addition, lung ODC became coupled to beta-adrenergic receptors prematurely in the dexamethasone group, suggesting that neural control of tissue differentiation is altered. These data indicate that prenatal glucocorticoids may compromise lung development through effects on cell replication and differentiation, which derive, in part, from alterations in the reception of trophic neural signals.
Navarro
H A
HA
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
Kudlacz
E M
EM
Eylers
J P
JP
Slotkin
T A
TA
D000818:Animals; D003907:Dexamethasone / Q000633:toxicity*; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D008168:Lung / Q000196:embryology* / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains
D003907:Dexamethasone; D009955:Ornithine Decarboxylase; D007545:Isoproterenol