RGD Reference Report - Expression of CYP3A23/1, CYP3A2, PXR, CAR and HNF4alpha in large-for-gestational-age neonatal rats. - Rat Genome Database

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Expression of CYP3A23/1, CYP3A2, PXR, CAR and HNF4alpha in large-for-gestational-age neonatal rats.

Authors: Ni, Shaoqing  Wang, Xiumin  Wang, Jue  Zeng, Su  Zhao, Zhengyan 
Citation: Ni S, etal., Pharmazie. 2009 Apr;64(4):252-7.
RGD ID: 12904767
Pubmed: (View Article at PubMed) PMID:19435144


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 HNF4alpha.
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 HNF4alpha 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. HNF4alpha 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 HNF4alpha-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 HNF4alpha, suggesting that further research on this issue is warranted.

Annotation

Disease Annotations    
Fetal Macrosomia  (IEP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Hnf4a  (hepatocyte nuclear factor 4, alpha)

Genes (Mus musculus)
Hnf4a  (hepatic nuclear factor 4, alpha)

Genes (Homo sapiens)
HNF4A  (hepatocyte nuclear factor 4 alpha)


Additional Information