Prenatal hormone treatment with thyrotropin releasing hormone and with thyrotropin releasing hormone plus dexamethasone delays antioxidant enzyme maturation but does not inhibit a protective antioxidant enzyme response to hyperoxia in newborn rat lung.
Whereas glucocorticoid administration to pregnant rats produces parallel acceleration of lung surfactant and antioxidant enzyme system maturation in late gestation, prenatal thyroid hormone treatment results in acceleration of surfactant maturation, with a paradoxical decrease in antioxidant enzyme (AOE) development. In these studies, we tested whether prenatal thyroid releasing hormone (TRH) treatment would act like prenatal thyroid hormone on pulmonary surfactant and AOE system maturation and whether combined prenatal treatment with TRH plus dexamethasone (DEX) would alter these effects. Secondly, we tested whether prenatal TRH and prenatal TRH plus DEX would inhibit the ability of newborn rats to respond to hyperoxia with protective increases in AOE activities. Results of the developmental studies revealed significantly increased fetal lung disaturated phosphatidylcholine content with significantly decreased pulmonary AOE activities as a result of prenatal TRH treatment that was not reversed with the addition of DEX. Combined TRH plus DEX treatment resulted in statistically significant decreases in body weight, lung weight, and lung weight to body weight ratios at both 21 and 22 d of gestation; growth effects were not seen with TRH alone. In terms of hyperoxic AOE response, despite being born with lower baseline AOE levels, the newborn animals prenatally treated with TRH or TRH plus DEX were able to induce a normal pulmonary AOE response to high O2 exposure. Although requiring further investigation, this reassuring finding suggests that clinical prenatal therapy with TRH or the combination of TRH plus DEX is not contraindicated for those infants delivered prematurely who go on to require intensive hyperoxic therapy.
Rodriguez
M P
MP
Department of Pediatrics, University of Miami School of Medicine, Florida 33101.
Sosenko
I R
IR
Antigua
M C
MC
Frank
L
L
D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000378:metabolism*; D003907:Dexamethasone / Q000008:administration & dosage*; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D005325:Fetal Organ Maturity / Q000187:drug effects; D005333:Fetus / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D010100:Oxygen; D011247:Pregnancy; D011663:Pulmonary Surfactants / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013973:Thyrotropin-Releasing Hormone / Q000008:administration & dosage*
D000975:Antioxidants; D011663:Pulmonary Surfactants; D013973:Thyrotropin-Releasing Hormone; D003907:Dexamethasone; D010100:Oxygen