Vitamin K-dependent carboxylase activity in fetal rat lung: developmental effects of dexamethasone and triiodothyronine.
Dexamethasone (Dex) and triiodothyronine (T3) were administered to pregnant rats during late gestation to evaluate potential developmental effects on fetal lung vitamin K-dependent carboxylation. Maternal rats were injected on the 2 d before study with Dex (0.2 mg/kg intraperitoneally), with T3 (0.7, 3.5, or 7 mg/kg intramuscularly), or with a combination of both hormones. Fetal lung microsomes were prepared at 18, 19, and 20 d of gestation, and carboxylase activity was assessed by measuring the incorporation of 14CO2 into a synthetic pentapeptide substrate. Dex alone resulted in a small but consistent increase in activity in all three gestational ages. T3 alone increased activity approximately 85% at 20 d of gestation. Treatment with a combination of Dex and T3 caused a 60% increase in vitamin K-dependent carboxylation at each gestational age. Decreased lung growth was noted with combination hormone treatment in all rats studied at 19 and 20 d of gestation. Lung growth expressed as lung wt/body wt was more sensitive to the effects of Dex plus T3 than was carboxylase activity. Decreased lung wt/body wt (decreased 25%) was noted with Dex plus T3 (0.7 mg/kg); however, no induction of carboxylase enzyme activity was evident at this dose. This study demonstrates that vitamin K-dependent carboxylase activity in fetal rat lung can be induced by the exogenous administration of Dex and T3 to pregnant rats. Fetal lung microsomes contain multiple endogenous substrates for the vitamin K-dependent carboxylase enzyme. These hormones play a significant developmental role not only in protein biosynthesis, but in posttranslational processing as well.(ABSTRACT TRUNCATED AT 250 WORDS)
Gallaher
K J
KJ
Department of Pediatrics, Pennsylvania State University, Milton S. Hershey Medical Center, Hershey 17033.
Rannels
D E
DE
Rannels
S R
SR
D000818:Animals; D019735:Carbon-Carbon Ligases; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005325:Fetal Organ Maturity / Q000187:drug effects; D005333:Fetus / Q000378:metabolism* / Q000502:physiology; D008025:Ligases / Q000378:metabolism*; D008168:Lung / Q000196:embryology* / Q000378:metabolism; D011247:Pregnancy; D011499:Protein Processing, Post-Translational; D011663:Pulmonary Surfactants / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014284:Triiodothyronine / Q000494:pharmacology*
D011663:Pulmonary Surfactants; D014284:Triiodothyronine; D003907:Dexamethasone; D008025:Ligases; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase