Effects of prenatal dexamethasone on development of ornithine decarboxylase activity in brain and peripheral tissues of rats.
The use of glucocorticoids in the management of neonatal respiratory distress syndrome may be associated with abnormalities of growth and neurologic development. In our study, pregnant rats received either 2 or 0.2 mg/kg of dexamethasone on gestational days 17, 18, and 19 and tissues of the offspring were examined for ornithine decarboxylase activity, a marker enzyme for perturbations of cellular maturation. Acutely, the higher dose of dexamethasone suppressed ornithine decarboxylase activity in all tissues except lung, where a short-term stimulation was obtained. Repeated administration of 2 mg/kg resulted in an ornithine decarboxylase pattern consistent with delayed cellular development in all tissues (suppressed activity followed by prolonged postnatal elevations), accompanied by impaired viability and general growth. Lowering the dose of dexamethasone to 0.2 mg/kg eliminated all the adverse effects on viability but still produced perturbations of tissue ornithine decarboxylase, most notably a prolonged suppression of activity across all brain regions. These data suggest that administration of glucocorticoids even at the threshold for effects on respiratory function, may compromise neural development.
Navarro
H A
HA
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
Lachowicz
J
J
Bartolome
J
J
Whitmore
W L
WL
Slotkin
T A
TA
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000196:embryology / Q000201:enzymology / Q000254:growth & development; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D009929:Organ Size / Q000187:drug effects; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D003907:Dexamethasone; D009955:Ornithine Decarboxylase