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

Martin Krøyer Rasmussen*, Carsten Scavenius, Sabine Gerbal-Chaloin, Jan Enghild

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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.

Original languageEnglish
JournalToxicology Letters
Volume314
Pages (from-to)181-186
Number of pages6
ISSN0378-4274
DOIs
Publication statusPublished - Oct 2019

Keywords

  • Animal model
  • Detoxification
  • Gender
  • In vitro
  • Liver
  • Porcine

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