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

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 R (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 5 0.002), 2A (P 5 0.000) and 2E1 (P 5 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 pigs, testicular steroids, liver, cytochrome P450 ImplicationsWe studied in vivo regulation of cytochrome P450 (CYP450) 1A, 2A and 2E1 activities in uncastrated male pigs with high concentrations of testicular steroids, and surgically and immunologically castrated pigs with low steroid concentrations. We confirmed an association between steroids and CYP450 expression. We suggest that this regulation occurs at the transcriptional level, as indicated by suppressed CYP450 mRNA in uncastrated pigs. This suppression was not always reflected in decreased activities, suggesting that at least some CYP450s (e.g. CYP2E1) are regulated by a post-transcriptional mechanism. These results contribute to the knowledge on porcine CYP450 and its in vivo regulation by testicular steroids.

Impact of age on hepatic cytochrome P450 of domestic male Camborough‐29 pigs

“…This activity is not detectable in the porcine liver microsomes at the age of 1 day and 2 weeks of intact males, but detected at a significant level in castrated males at the age of 5 weeks, and then rapidly increases with growth. This is consistent with the significant increase in CYP2A mRNA expression, protein, and enzyme activity levels after removal of the primary androgen source (Gillberg et al ., ; Chen et al ., ; Zamaratskaia et al ., ; Brunius et al ., ) in addition to the age effect.…”

Influence of sex and immunocastration on feed intake behavior, skatole and indole concentrations in adipose tissue of pigs

“…In immunocastrates with an overall high feed intake rate significantly higher indole concentrations were measured than in all other groups. It is known that the levels of enzymes that are involved in the degradation of skatole (CYP2E1 and CYP2A) are increased in barrows and immunocastrates when compared with the levels in boars (Zamaratskaia et al, 2009;Brunius et al, 2012). In vitro studies with porcine hepatocytes revealed that the addition of androstenone in physiological amounts reduced the activity of both enzymes (Doran et al, 2002b;Rasmussen et al, 2011).…”

Feeding dried chicory root to pigs decrease androstenone accumulation in fat by increasing hepatic 3β hydroxysteroid dehydrogenase expression

“…Kojima et al [8] showed that administration of testosterone propionate to pigs decreased the expression of CYP1A. The suggestion that CYP450 expression in pigs is affected by steroids is further supported by studies showing difference in CYP450 expression/activity with respect to gender [9][10][11][12][13], castration [14] and immunocastration (active immunization against GnRH) [11,15]. These studies provide strong evidence that androgens and estrogens have a down-regulating effect on CYP450 expression and activity.…”