Altered gene level expression of thyroid hormone receptors alpha-1 and beta-1 in the lung of nitrofen-induced diaphragmatic hernia

Purpose: Thyroid receptor alpha-1 (TR-alpha1) and thyroid receptor beta-1 ( TR-beta1) are thought to be essential for the feta I and postnatal developm ent of the lung. The authors investigated gene level expression of TR-alpha 1 and TR-beta1 in the lung of nitrofen-induced congenital diaphragmatic her nia (CDH) using reverse transcription polymerase chain reaction (RT-PCR). Methods: CDH was induced in pregnant rats after administration of 100 mg ni trofen 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 wer e 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 nit rofen-treated without CDH lung (2.232 +/- 0.193; (P < .05). TR-beta1 mRNA e xpression also was significantly decreased in CDH lung (2.223 +/- 0.270) co mpared with controls (3.569 +/- 0.262; P < .01) and nitrofen-treated withou t CDH lung (3.235 +/- 0.299; P < .05). Conclusion: These data suggest that the downregulation of thyroid hormone s ignaling pathway through altered expression of TR-alpha1 and TR-beta1 durin g lung morphogenesis may be a contributory factor in the pathogenesis of pu lmonary hypoplasia in nitrofen-induced CDH. J Pediatr Surg 36:1675-1678. Co pyright (C) 2001 by W.B. Saunders Company.