Fetal dexamethasone exposure affects basal ornithine decarboxylase activity in developing rat brain regions and alters acute responses to hypoxia and maternal separation.
Although glucocorticoids are widely used to stimulate fetal/neonatal lung function, they also interfere with cellular development in the central nervous system. Dexamethasone was administered to pregnant rats in late gestation at a dose (0.8 mg/kg) that lies just above the threshold for stimulation of lung surfactant synthesis, and the impact on ornithine decarboxylase (ODC) was evaluated in three brain regions. Dexamethasone treatment produced an initial inhibition of basal ODC activity followed by postnatal elevations, a pattern known to be associated with delays in cell replication and differentiation. Dexamethasone also interfered with the ability of the 1-day-old neonate to turn off ODC acutely in response to a 2-h period of maternal separation; as this response conserves energy in the absence of the dam, the effect of dexamethasone is maladaptive. Additionally, dexamethasone sensitized the neonatal brain to hypoxia: the acute increase of ODC associated with a 2-h exposure to 7% O2 was exacerbated in 8-day-old rats exposed to dexamethasone prenatally. These results suggest that administration of dexamethasone, in doses that promote respiratory competence, delays cell development in the central nervous system and renders the brain more vulnerable to adverse neonatal conditions, such as maternal separation or hypoxia.
Carlos
R Q
RQ
Department of Pediatrics, Duke University Medical Center, Durham, N.C.
Seidler
F J
FJ
Lappi
S E
SE
Slotkin
T A
TA
D000818:Animals; D001933:Brain Stem / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005325:Fetal Organ Maturity / Q000187:drug effects; D005328:Fetal Viability / Q000187:drug effects; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D008426:Maternal Deprivation; D008636:Mesencephalon / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats
D003907:Dexamethasone; D009955:Ornithine Decarboxylase