Hostname: page-component-586b7cd67f-r5fsc Total loading time: 0 Render date: 2024-11-30T20:35:04.607Z Has data issue: false hasContentIssue false
  • English
  • Français

Expression and activities of hepatic cytochrome P450 (CYP1A, CYP2A and CYP2E1) in entire and castrated male pigs

Published online by Cambridge University Press:  22 September 2011

C. Brunius ,
M. K. Rasmussen ,
H. Lacoutière ,
K. Andersson ,
B. Ekstrand  and
G. Zamaratskaia
C. Brunius*
Affiliation:
Department of Food Science, Swedish University of Agricultural Sciences (SLU), PO Box 7051, S-750 07 Uppsala, Sweden
M. K. Rasmussen
Affiliation:
Department of Food Science, Aarhus University, PO Box 50, DK-8830 Tjele, Denmark
H. Lacoutière
Affiliation:
Department of Food Science, Swedish University of Agricultural Sciences (SLU), PO Box 7051, S-750 07 Uppsala, Sweden
K. Andersson
Affiliation:
Department of Animal Nutrition and Management, Swedish University of Agricultural Sciences (SLU), PO Box 7024, S-750 07 Uppsala, Sweden
B. Ekstrand
Affiliation:
Department of Food Science, Aarhus University, PO Box 50, DK-8830 Tjele, Denmark
G. Zamaratskaia
Affiliation:
Department of Food Science, Swedish University of Agricultural Sciences (SLU), PO Box 7051, S-750 07 Uppsala, Sweden
*
†Email: [email protected]
Get access

Abstract

This study aimed to provide further insights into the mechanism of in vivo regulation of cytochrome P450 (CYP450) 1A, 2A and 2E1 activities in pigs with different levels of testicular steroids. Hepatic mRNA and protein expression and enzymatic activity of CYP1A, CYP2A and CYP2E1 were compared between entire male and castrated pigs. Castration was performed either surgically or immunologically. The pigs were divided into four groups. In the first group, piglets were surgically castrated without anaesthesia. Immunological castration was performed by vaccination with Improvac® (Pfizer Ltd). Vaccinated pigs were subdivided into two groups according to the vaccination regimen: early and standard vaccination. Pigs in the early vaccination group were vaccinated when aged 11 and 15 weeks. Pigs in the standard vaccination group were vaccinated when aged 17 and 21 weeks. In the control group, pigs remained intact throughout the study. Hepatic CYP450 mRNA expression, measured by real-time RT-PCR, differed significantly between groups for all isoforms measured: CYP1A2 (P = 0.002), 2A (P = 0.000) and 2E1 (P = 0.002). Lower CYP450 mRNA in entire male pigs suggests suppression of CYP1A2, CYP2A and CYP2E1 by testicular steroids at the transcriptional level. However, this suppression was not always reflected in decreased protein expression and activities of these isoforms, suggesting that at least some CYP450s (e.g. CYP2E1) are regulated by a post-transcriptional mechanism.

Keywords

male pigstesticular steroidslivercytochrome P450
Type
Full Paper
Information
animal , Volume 6 , Issue 2 , 03 January 2012 , pp. 271 - 277
Copyright
Copyright © The Animal Consortium 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Andersson, K, Brunius, C, Zamaratskaia, G, Lundström, K 2011. Early vaccination with Improvac® – effects on performance and behaviour of male pigs. Animal (in press), doi:10.1017/S1751731111001200.Google Scholar
Andersson, K, Schaub, A, Andersson, K, Lundström, K, Thomke, S, Hansson, I 1997. The effects of feeding system, lysine level and gilt contact on performance, skatole levels and economy of entire male pigs. Livestock Production Science 51, 131–140.CrossRefGoogle Scholar
Chen, G, Cue, RA, Lundström, K, Wood, JD, Doran, O 2008. Regulation of CYP2A6 protein expression by skatole, indole, and testicular steroids in primary cultured pig hepatocytes. Drug Metabolism and Disposition 36, 56–60.CrossRefGoogle ScholarPubMed
Doran, E, Whittington, FW, Wood, JD, McGivan, JD 2002a. Cytochrome P450IIE1 (CYP2E1) is induced by skatole and this induction is blocked by androstenone in isolated pig hepatocytes. Chemico-Biological Interactions 140, 81–92.CrossRefGoogle ScholarPubMed
Doran, E, Whittington, FW, Wood, JD, McGivan, JD 2002b. The relationship between adipose tissue skatole levels, rates of hepatic microsomal skatole metabolism and hepatic cytochrome P450IIE1 expression in two breeds of pig. Animal Science 74, 461–468.CrossRefGoogle Scholar
Einarsson, S, Brunius, C, Wallgren, M, Lundström, K, Andersson, K, Zamaratskaia, G, Rodriguez-Martinez, H 2011. Effects of early vaccination with Improvac® on the development and function of reproductive organs of male pigs. Animal Reproduction Science (in press), doi:10.1016/j.anireprosci.2011.06.006.CrossRefGoogle ScholarPubMed
Gillberg, M, Skaanild, MT, Friis, C 2006. Regulation of gender-dependent CYP2A expression in pigs: involvement of androgens and CAR. Basic and Clinical Pharmacology and Toxicology 98, 480–487.CrossRefGoogle ScholarPubMed
Kocarek, TA, Zangar, RC, Novak, RF 2000. Post-transcriptional regulation of rat CYP2E1 expression: role of CYP2E1 mRNA untranslated regions in control of translational efficiency and message stability. Archives of Biochemistry and Biophysics 376, 180–190.CrossRefGoogle ScholarPubMed
Kojima, M, Sekimoto, M, Degawa, M 2008. A novel gender-related difference in the constitutive expression of hepatic cytochrome P4501A subfamily enzymes in Meishan pigs. Biochemical Pharmacology 75, 1076–1082.CrossRefGoogle ScholarPubMed
Lin, Z, Lou, Y, Squires, EJ 2004. Molecular cloning, expression and functional characterization of the cytochrome P450 2A6 gene in pig liver. Animal Genetics 35, 314–316.CrossRefGoogle ScholarPubMed
Lin, Z, Lou, Y, Squires, EJ 2006. Functional polymorphism in porcine CYP2E1 gene: its association with skatole levels. Journal of Steroid Biochemistry and Molecular Biology 99, 231–237.CrossRefGoogle ScholarPubMed
Metz, C, Claus, R 2003. Active immunization of boars against GnRH does not affect growth hormone but lowers IGF-I in plasma. Livestock Production Science 81, 129–137.CrossRefGoogle Scholar
Owens, PC, Gatford, KL, Walton, PE, Morley, W, Campbel, RG 1999. The relationship between endogenous insulin-like growth factors and growth in pigs. Journal of Animal Science 77, 2098–2103.CrossRefGoogle ScholarPubMed
Rasmussen, MK, Ekstrand, B, Zamaratskaia, G 2011a. Comparison of cytochrome P450 concentrations and metabolic activities in porcine hepatic microsomes prepared with two different methods. Toxicology in Vitro 25, 343–346.CrossRefGoogle ScholarPubMed
Rasmussen, MK, Zamaratskaia, G, Ekstrand, B 2011b. In vitro cytochrome P450 2E1 and 2A activities in the presence of testicular steroids. Reproduction in Domestic Animals 46, 149–154.CrossRefGoogle ScholarPubMed
Rasmussen, MK, Zamaratskaia, G, Ekstrand, B 2011c. In vivo effect of dried chicory root (Cichorium intybus L.) on xenobiotica metabolising cytochrome P450 enzymes in porcine liver. Toxicology Letters 200, 88–91.CrossRefGoogle Scholar
Rasmussen, MK, Zamaratskaia, G, Ekstrand, B 2011d. Gender-related differences in cytochrome P450 in porcine liver – implication for activity, expression and inhibition by testicular steroids. Reproduction in Domestic Animals 46, 616–623.CrossRefGoogle ScholarPubMed
Skaanild, MT, Friis, C 2007. Is bupropion a more specific substrate for porcine CYP2E than chlorzoxazone and p-nitrophenol? Basic and Clinical Pharmacology and Toxicology 101, 159–162.CrossRefGoogle ScholarPubMed
Skinner, TM, Doran, E, McGivan, JD, Haley, CS, Archibald, AL 2005. Cloning and mapping of the porcine cytochrome-p450 2E1 gene and its association with skatole levels in the domestic pig. Animal Genetics 36, 417–422.CrossRefGoogle ScholarPubMed
Tambyrajah, WS, Doran, E, Wood, JD, McGivan, JD 2004. The pig CYP2E1 promoter is activated by COUP-TF1 and HNF-1 and is inhibited by androstenone. Archives of Biochemistry and Biophysics 431, 252–260.CrossRefGoogle ScholarPubMed
Whittington, FM, Nute, GR, Hughes, SI, McGivan, JD, Lean, IJ, Wood, JD, Doran, E 2004. Relationships between skatole and androstenone accumulation, and cytochrome P4502E1 expression in Meishan × Large White pigs. Meat Science 67, 569–576.CrossRefGoogle Scholar
Zamaratskaia, G, Squires, EJ 2009. Biochemical, nutritional and genetic effects on boar taint in entire male pigs. Animal 3, 1508–1521.CrossRefGoogle ScholarPubMed
Zamaratskaia, G, Zlabek, V 2009. EROD and MROD as markers of cytochrome P450 1A activities in hepatic microsomes from entire and castrated male pigs. Sensors 9, 2134–2147.CrossRefGoogle ScholarPubMed
Zamaratskaia, G, Chen, G, Lundström, K 2006. Effects of sex, weight, diet and hCG administration on levels of skatole and indole in the liver and hepatic activities of cytochromes P4502E1 and P4502A6 in pigs. Meat Science 72, 331–338.CrossRefGoogle ScholarPubMed
Zamaratskaia, G, Gilmore, WJ, Lundström, K, Squires, EJ 2007. Effect of testicular steroids on catalytic activities of cytochrome P450 enzymes in porcine liver microsomes. Food and Chemical Toxicology 45, 676–681.CrossRefGoogle ScholarPubMed
Zamaratskaia, G, Zlabek, V, Chen, G, Madej, A 2009. Modulation of porcine cytochrome P450 enzyme activities by surgical castration and immunocastration. Animal 3, 1124–1132.CrossRefGoogle ScholarPubMed
Zamaratskaia, G, Rasmussen, MK, Herbin, I, Ekstrand, B, Zlabek, V 2011. In vitro inhibition of porcine cytochrome P450 by 17β-estradiol and 17α-estradiol. Interdisciplinary Toxicology 4, 101–107.CrossRefGoogle ScholarPubMed
Zamaratskaia, G, Oskam, IC, Ropstad, E, Tajet, H, Dahl, E, Andresen, O 2008. Effects of hCG stimulation on hepatic activities of cytochromes P4502E1 and P4502A in pubertal male pigs. Reproduction in Domestic Animals 43, 147–152.CrossRefGoogle ScholarPubMed