Glucocorticoid regulation of ornithine decarboxylase in the postnatal rat lung.
Ornithine decarboxylase (ODC) is thought to play a critical role in pulmonary development. The purpose of this study was to characterize the effects of dexamethasone on ODC gene expression and enzyme activity in the lung of rat pups. Subcutaneous administration of dexamethasone (10 mg/kg) was shown to suppress ODC activity in 2-, 6- and 10-day-old rats for as long as 24 h after injection. In contrast, dexamethasone treatment stimulated liver ODC activity indicating that the inhibition of lung ODC is tissue specific. Contrary to expectation, the glucocorticoid enhanced lung ODC expression as indicated by an increased accumulation of ODC mRNA transcripts. The latter effect was associated with an heightened expression of c-myc and max mRNAs, the encoded proteins of which act as transactivators of the ODC gene. Dexamethasone did not alter lung levels of"antizyme" (AZ), an inducible protein that specifically promotes the degradation of the ODC protein enzyme. However, the lack of AZ induction does not necessarily mean that ODC degradation is not the mechanism for the decrease in lung ODC activity of dexamethasone-treated animals. The results obtained indicate that glucocorticoids can downregulate lung ODC activity, and that the effect is mediated by post-transcriptional rather than transcriptional mechanisms. These findings are consistent with the idea that endogenous glucocorticoids play an important role in the modulation of ODC activity and early pulmonary development.
Bartolome
J V
JV
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA. jvb@acpub.duke.edu
Wang
S
S
Greer
N L
NL
Schanberg
S M
SM
D000818:Animals; D000831:Animals, Newborn; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D016259:Genes, myc; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D009955:Ornithine Decarboxylase / Q000235:genetics / Q000378:metabolism*; D051381:Rats
D003907:Dexamethasone; D009955:Ornithine Decarboxylase