Positive regulation of pulmonary antioxidant enzyme gene expression by prenatal thyrotropin releasing hormone plus dexamethasone treatment in premature rats exposed to hyperoxia.
Prenatal administration of thyrotropin releasing hormone (TRH) plus dexamethasone (DEX) to pregnant rats produces significantly depressed fetal lung antioxidant enzyme (AOE) activities and AOE mRNA levels in late gestation. Because of this negative regulation of AOE gene expression in the late fetal lung, we hypothesized that hormonally pretreated prematurely delivered rats might demonstrate inferior tolerance to prolonged hyperoxia. Litters of prenatal TRH+DEX-treated and sham-treated prematurely delivered rat pups (gestational d 21 of 22) were randomized to either > 95% O2 or room air for up to 14 d. The right lungs of 2- and 7-d exposure pups were assayed for AOE activities; the left lungs of the same pups were used to quantitate the concentrations of AOE mRNA by solution hybridization. The prenatal TRH+DEX-treated pups were able to induce adaptive lung AOE mRNA and activity responses to hyperoxia by 2 d of exposure; and by 7 d in O2 they showed greater increases in AOE mRNA concentrations and AOE activities in response to hyperoxic challenge compared with the sham-treated controls. Lung lipid surfactant measurements after hyperoxia were not affected by prenatal TRH+DEX treatment. In addition, TRH+DEX-pretreated premature rats did not show the hypothesized increased susceptibility to O2-induced lung damage and lethality, but, in fact, had slightly improved hyperoxic survival (d 3-7 of O2 exposure) compared with sham-treated controls. Exposure to hyperoxia significantly reduced serum triiodothyronine and thyroxine levels in the sham-control pups.(ABSTRACT TRUNCATED AT 250 WORDS)
Chen
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Department of Pediatrics, University of Miami School of Medicine, Florida 33101, USA.
Sosenko
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IR
Frank
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D000818:Animals; D000975:Antioxidants; D002374:Catalase / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005979:Glutathione Peroxidase / Q000235:genetics; D018496:Hyperoxia / Q000196:embryology / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000196:embryology / Q000201:enzymology*; D008297:Male; D010544:Peroxidases / Q000235:genetics*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000235:genetics*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D000975:Antioxidants; D014284:Triiodothyronine; D013973:Thyrotropin-Releasing Hormone; D003907:Dexamethasone; D010544:Peroxidases; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D013974:Thyroxine