Expression of CYP3A23/1, CYP3A2, PXR, CAR and HNF4α in large-for-gestational-age neonatal rats

Background: The available information about hepatic drug-metabolizing enzymes in the large-for-gestational-age (LGA) neonate is limited. Objective: To determine whether LGA status alters expression of the cytochrome p450 enzymes, CYP3A23/1 and CYP3A2, and nuclear receptors PXR, CAR and HNF4α. Methods: Appropriate-for-gestational-age (AGA) and LGA pups from 10 litters of rats (n = 15 pups/group) were used. Hepatic expression levels of CYP3A23/1, CYP3A2, pregnane X receptor (PXR), constitutive androstane receptor (CAR), and HNF4α mRNA were detected by quantitative real-time RT-PCR. Protein expression was determined immunohistochemically and expression levels were evaluated using staining intensity scores and percentage of positive hepatocytes. Results: The mean body weights of AGA and LGA rat pups were 6.20 ± 0.49 and 7.77 ± 0.70 g (mean ± SD), respectively (P < 0.001). Liver weight/body weight ratios trended higher in the LGA group (5.18 ± 0.50%, mean ± SD) than in the AGA group (4.90 ± 0.01%, mean ± SD), but the difference was not significant. CYP3A2 mRNA levels were higher in LGA than in AGA pups (P < 0.05), but there were no group differences in CYP3A23/1 mRNA levels. HNF4α levels were also higher in the LGA group (P < 0.05), but PXR and CAR mRNA levels did not differ between the groups. The staining intensity and frequency of CYP3A23/1-positive and HNF4α-positive hepatocytes differed between LGA and AGA pups, whereas no significant differences in CYP3A2 or CAR protein expression were observed between groups. Conclusions: LGA status affects the hepatic expression of CYP3A23/1, CYP3A2, and HNF4α, suggesting that further research on this issue is warranted.