Role of ornithine decarboxylase and polyamines in early postnatal lung growth.
We assessed the importance of ornithine decarboxylase (ODC) and polyamines in early postnatal lung growth. Lung-ODC activity in newborn rats rose rapidly after birth and was highest at 4-6 days of age. Lung putrescine and spermidine specific contents also peaked during this period, but spermine specific content remained relatively unchanged. The temporal pattern of these changes differed markedly from that in the heart, brain, and kidney where ODC activity is highest at birth then rapidly declines. The period of peak lung-ODC activity and polyamine specific content correlated with rapid increases in lung DNA content, protein content, and weight. The specific irreversible ODC inhibitor, alpha-difluoromethylornithine, significantly reduced lung-ODC activity and putrescine and spermidine specific content; it also caused significant early reductions in lung DNA and protein content without simultaneously affecting body weight and appearance. Morphometrically, the lungs of alpha-difluoromethylornithine-treated rats had significantly fewer type 2 epithelial cells, interstitial cells, and capillary endothelial cells than the lungs of controls. We conclude that ODC and polyamines play an important role in postnatal lung growth and that alpha-difluoromethylornithine can be used as a probe to disrupt lung growth.
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development*; D004247:DNA / Q000378:metabolism; D000518:Eflornithine / Q000494:pharmacology; D008168:Lung / Q000033:anatomy & histology / Q000187:drug effects / Q000254:growth & development*; D009929:Organ Size / Q000187:drug effects; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D011700:Putrescine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013095:Spermidine / Q000378:metabolism
D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D011506:Proteins; D004247:DNA; D009955:Ornithine Decarboxylase; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine