Sex dictates the constitutive expression of hepatic cytochrome P450 isoforms in Göttingen minipigs. (10th October 2019)

• Record Type: Journal Article
• Authors: Rasmussen, Martin Krøyer; Scavenius, Carsten; Gerbal-Chaloin, Sabine; Enghild, Jan
• Is Part Of: Toxicology letters. Volume 314(2019)
• Page Start: 181
• Page End: 186
• Publication Date: 2019-10-10
• Subjects: Detoxification -- Gender -- Animal model -- Liver -- In vitro -- Porcine; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2019.08.008
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: The cytochrome p450 expression is influenced by sex in Göttingen minipigs. Female minipigs shows greater expression of cytochrome p450. CYP3A, CYP2C and CYP2D are the most abundant subfamilies in Göttingen minipigs. 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.