The pig CYP2E1 promoter is activated by COUP-TF1 and HNF-1 and is inhibited by androstenone

Tambyrajah, Winston S.; Doran, Elena; Wood, J. D.; McGivan, J D

doi:10.1016/j.abb.2004.08.016

Cited by 46 publications

(46 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, a better understanding of the regulation of the expression of this gene might help to identify other candidate genes [13]. Tambyrajah et al [46] have exploited the recent sequencing of the 5' flanking region of the CYP2E1 gene to characterize factors regulating the CYP2E1 promoter activity. They have demonstrated that in pig, binding of two transcription factors (HNF-1 and COUP-TF1) to CYP2E1 could activate the promoter.…”

Section: Phase I Metabolismmentioning

confidence: 99%

“…However, a second hypothesis considering that androgens inhibit the catabolism of skatole has been more widely investigated [13]. Tambyrajah et al [46] have proposed that regulation mechanisms acting on the promoter of the CYP2E1 gene are very important to explain the variability of skatole level in fat. They have shown that androstenone can inhibit the binding of COUP-TF1 to the promoter of the CYP2E1 gene.…”

Section: Relationship Between Androstenone and Skatole Levelsmentioning

confidence: 99%

See 1 more Smart Citation

Genetic and metabolic aspects of androstenone and skatole deposition in pig adipose tissue: A review(Open Access publication)

Robic

Larzul²,

Bonneau³

2007

Genet. Sel. Evol.

View full text Add to dashboard Cite

-High levels of androstenone and skatole in fat tissues are considered the primary causes of boar taint, an unpleasant odour and flavour of the meat from non-castrated male pigs. The aim of this article is to review our current knowledge of the biology and genetic control of the accumulation of androstenone and skatole in fat tissue. Two QTL mapping studies have shown the complexity of the genetic control of these traits. During the last ten years, several authors have taken a more physiological approach to investigate the involvement of genes controlling the metabolism of androstenone and skatole. Although some authors have claimed the identification of candidate genes, it is more appropriate to talk about target genes. This suggests that genes affecting androstenone and skatole levels will have to be sought for among specific or non-specific transcription factors interacting with these target genes.androstenone / skatole / pig / boar taint / QTL

show abstract

Section: Phase I Metabolismmentioning

confidence: 99%

Section: Relationship Between Androstenone and Skatole Levelsmentioning

confidence: 99%

Genetic and metabolic aspects of androstenone and skatole deposition in pig adipose tissue: A review(Open Access publication)

Robic

Larzul²,

Bonneau³

2007

Genet. Sel. Evol.

View full text Add to dashboard Cite

show abstract

“…Castrated pigs are known to have higher activities of a number of CYP450 isoforms . It is likely that the higher CYP450 activity (for at least some isoforms) is due to the absence or low levels of testicular steroids, which otherwise inhibit CYP450 expression at the level of transcription (Tambyrajah et al, 2004;Gillberg et al, 2006;Kojima et al, 2008). Moreover, testicular steroids, particularly androstenone and oestradiol, are directly involved in the regulation of CYP2E1 activities (Zamaratskaia et al, 2007 andRasmussen et al, 2011b).…”

Section: Discussionmentioning

confidence: 99%

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

Brunius

Rasmussen

Lacoutière

et al. 2012

Animal

View full text Add to dashboard Cite

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.

show abstract

“…Additionally, androstenone modified CYP2A6 protein expression and down-regulated the skatole-induced expression of CYP2E1 in primary cultured pig hepatocytes (Doran et al, 2002). Tambyrajah et al (2004) reported that androstenone decreases CYP2E1 promoter activity by inhibiting the binding of a transcription factor. If the genes are regulated at the transcriptional level, it is not surprising that little or no inhibitory effect of steroids was observed at the protein level in the present study.…”

Section: Discussionmentioning

confidence: 99%

Modulation of porcine cytochrome P450 enzyme activities by surgical castration and immunocastration

Zamaratskaia

Žlábek

Chen

et al. 2009

Animal

View full text Add to dashboard Cite

The present study aimed to evaluate some cytochrome P450 metabolic enzyme activities in hepatic microsomes prepared from entire male pigs (uncastrated pigs), surgically castrated pigs and pigs immunized against gonadotropin-releasing hormone (immunocastrated pigs). The activities of the following enzymes were measured: ethoxyresorufin O-deethylase (EROD, CYP1A1/ 1A2), methoxyresorufin O-deethylase (MROD, CYP1A2), pentoxyresorufin O-depentylase (PROD, CYP2B), coumarin hydroxylase (COH, CYP2A) and p-nitrophenol hydroxylase (PNPH, CYP2A/2E1). The total cytochrome P450 contents were not affected by either surgical or immunocastration. Hepatic microsomal activities for EROD, PROD, COH and PNPH were lower in entire male pigs compared with surgically castrated and immunocastrated pigs ( P , 0.05). Surgically and immunocastrated male pigs were similar with respect to EROD, MROD, PROD and COH activities ( P . 0.05), whereas surgically castrated pigs exhibited lower PNPH activity compared with immunocastrated pigs ( P 5 0.029). The effect of different concentrations of testicular steroidstestosterone, 17b-estradiol, free estrone and androstenone -on enzyme activities was evaluated by in vitro microsomal study. Testosterone at the concentration of 8 pmol/ml inhibited EROD activities and estradiol-17b at the concentration of 1.8 pmol/ml inhibited PROD activities in hepatic microsomes from surgically castrated pigs. The highest concentration of androstenone (7520 pmol/ml) inhibited COH activities, whereas a 42-fold lower concentration of androstenone (180 pmol/ml) stimulated COH activities in surgically castrated pigs. Both free estrone (3.5 pmol/ml) and androstenone (55 pmol/ml) inhibited EROD activities in microsomes from entire male pigs. Stimulation of COH activities by the highest dose of free estrone (18 pmol/ml) was recorded in microsomes from entire male pigs. However, these effects of steroids were not concentration-dependent and the maximum extent did not exceed 615% variation compared with the controls. There was no inhibition of PNPH activities in the hepatic microsomes from either entire or castrated pigs. In conclusion, we showed that EROD, PROD, COH and PNPH activities were lower in entire male pigs compared with those in surgically and immunocastrated pigs. Direct inhibition by the testicular steroids -testosterone, 17b-estradiol, free estrone and androstenone -was not the primary cause of the reduced enzyme activities.Keywords: castration, cytochrome P450, porcine liver microsomes, steroids ImplicationsThe present study evaluated some cytochrome P450 enzyme activities in liver microsomes from uncastrated male pigs, surgically castrated pigs and pigs immunized against gonadotropin-releasing hormone (immunocastrated pigs). We found that CYP1A1, CYP2A, CYP2B and CYP2E1 activities were lower in uncastrated male pigs compared with surgically castrated and immunocastrated pigs. These findings strengthen the hypothesis of testicular steroid involvement in cytochrome P450 enzyme regulation. The differences in the ac...

show abstract

The pig CYP2E1 promoter is activated by COUP-TF1 and HNF-1 and is inhibited by androstenone

Cited by 46 publications

References 20 publications

Genetic and metabolic aspects of androstenone and skatole deposition in pig adipose tissue: A review(Open Access publication)

Genetic and metabolic aspects of androstenone and skatole deposition in pig adipose tissue: A review(Open Access publication)

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

Modulation of porcine cytochrome P450 enzyme activities by surgical castration and immunocastration

Contact Info

Product

Resources

About