Altered gene level expression of thyroid hormone receptors alpha-1 and beta-1 in the lung of nitrofen-induced diaphragmatic hernia.
OBJECTIVE
Thyroid receptor alpha-1 (TR-alpha1) and thyroid receptor beta-1 (TR-beta1) are thought to be essential for the fetal and postnatal development of the lung. The authors investigated gene level expression of TR-alpha1 and TR-beta1 in the lung of nitrofen-induced congenital diaphragmatic hernia (CDH) using reverse transcription polymerase chain reaction (RT-PCR).


METHODS
CDH was induced in pregnant rats after administration of 100 mg nitrofen on day 9.5 of gestation. Cesarean section was performed on day 21 of gestation. The fetuses were divided into 3 groups: normal controls (n = 16), nitrofen-induced CDH (n = 16), and nitrofen-treated without CDH (n = 16). mRNA was extracted from the left lung in each group. RT-PCR was performed to evaluate mRNA expressions of TR-alpha1 and TR-beta1. Levels of mRNA were expressed as a ratio of the band density divided by that of beta-actin, a house-keeping gene.


RESULTS
TR-alpha1 mRNA expression was decreased significantly in CDH lung (1.618 +/- 0.148) compared with controls (2.658 +/- 0.251; P <.01) and nitrofen-treated without CDH lung (2.232 +/- 0.193; (P <.05). TR-beta1 mRNA expression also was significantly decreased in CDH lung (2.223 +/- 0.270) compared with controls (3.569 +/- 0.262; P <.01) and nitrofen-treated without CDH lung (3.235 +/- 0.299; P <.05).


CONCLUSIONS
These data suggest that the downregulation of thyroid hormone signaling pathway through altered expression of TR-alpha1 and TR-beta1 during lung morphogenesis may be a contributory factor in the pathogenesis of pulmonary hypoplasia in nitrofen-induced CDH.
Teramoto
H
H
Children's Research Centre, Our Lady's Hospital for Sick Children, Dublin, Ireland.
Guarino
N
N
Puri
P
P
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006540:Herbicides; D006548:Hernia, Diaphragmatic / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000002:abnormalities* / Q000196:embryology / Q000378:metabolism*; D009024:Morphogenesis; D010647:Phenyl Ethers; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004268:DNA-Binding Proteins; D006540:Herbicides; D010647:Phenyl Ethers; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011988:Receptors, Thyroid Hormone; C007350:nitrofen