Sex dictates the constitutive expression of hepatic cytochrome P450 isoforms in Göttingen minipigs

Toxicol Lett. 2019 Oct 10;314:181-186. doi: 10.1016/j.toxlet.2019.08.008. Epub 2019 Aug 9.

Abstract

The cytochrome P450 enzyme (CYP) family includes key enzymes for the metabolism of drugs and xenobiotics. Several animal models have been used to determine the metabolite profile of specific drugs. Among these are porcine microsomes prepared from Göttingen minipigs. However, CYP expression profile in microsomes from this pig breed is unknown. In the present study, we determined the mRNA and protein profiles of a comprehensive selection of CYPs in microsomes prepared from male and female Göttingen minipigs. Using RT-PCR, western blotting and mass spectroscopy, we found that the expression levels of CYP1A, CYP2A and CYP2E1 were significantly higher in females than males. Moreover, some of the transcription factors controlling CYP transcription also showed a sex-dependent expression pattern. Conversely, expression of CYP2B, CYP2D and CYP3A was comparable between sexes. The overall CYP expression distribution showed high similarity with what previously been reported in humans. In conclusion, our results suggest that Göttingen minipigs are a reliable model for studying CYPs.

Keywords: Animal model; Detoxification; Gender; In vitro; Liver; Porcine.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism*
  • Female
  • Gene Expression Regulation, Enzymologic
  • Isoenzymes
  • Liver / enzymology*
  • Male
  • Microsomes / enzymology
  • Models, Animal
  • Sex Factors
  • Substrate Specificity
  • Swine
  • Swine, Miniature

Substances

  • Isoenzymes
  • Cytochrome P-450 Enzyme System