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

TY - JOUR

T1 - Sex dictates the constitutive expression of hepatic cytochrome P450 isoforms in Göttingen minipigs

AU - Rasmussen, Martin Krøyer

AU - Scavenius, Carsten

AU - Gerbal-Chaloin, Sabine

AU - Enghild, Jan

PY - 2019/10

Y1 - 2019/10

N2 - 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.

AB - 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.

KW - Animal model

KW - Detoxification

KW - Gender

KW - In vitro

KW - Liver

KW - Porcine

UR - http://www.scopus.com/inward/record.url?scp=85070700449&partnerID=8YFLogxK

U2 - 10.1016/j.toxlet.2019.08.008

DO - 10.1016/j.toxlet.2019.08.008

M3 - Journal article

C2 - 31404594

AN - SCOPUS:85070700449

SN - 0378-4274

VL - 314

SP - 181

EP - 186

JO - Toxicology Letters

JF - Toxicology Letters

ER -