A correlation study of Boar taint-related genes, Boar tant substances and sex hormones in Bama miniature pigs at defferent ages

Wang, Q. H.; Chen, J. Y.; Guo, Kenan; Zheng, Xiaokun; Wu, Qing; Wei, Hong; Liu, Y.

doi:10.18805/ijar.5962

Cited by 2 publications

(1 citation statement)

References 26 publications

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“…non-castrated, male pigs compared to surgically and immunologically castrated male pigs from Meishan (Kojima et al, 2008), Yorkshire x Landrace (Brunius et al, 2012) and Large White x Landrace x Duroc (Kubešová et al, 2019) strains. In entire Bama miniature male pigs, a decrease of CYP2A19 and CYP2E1 mRNA expression was observed after 6 months due to sexual maturity (Wang et al, 2015). However, suppressed CYP mRNA expression did not always result in decreased CYP protein and enzyme activity (e.g.…”

Section: Sex-related Differences In Cyp Protein Abundance In the Developing Göttingen Minipigmentioning

confidence: 98%

Hepatic Cytochrome P450 Abundance and Activity in the Developing and Adult Göttingen Minipig: Pivotal Data for PBPK Modeling

et al. 2021

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The Göttingen Minipig is gaining ground as nonrodent species in safety testing of drugs for pediatric indications. Due to developmental changes in pharmacokinetics and pharmacodynamics, physiologically based pharmacokinetic (PBPK) models are built to better predict drug exposure in children and to aid species selection for nonclinical safety studies. These PBPK models require high quality physiological and ADME data such as protein abundance of drug metabolizing enzymes. These data are available for man and rat, but scarce for the Göttingen Minipig. The aim of this study was to assess hepatic cytochrome P450 (CYP) protein abundance in the developing Göttingen Minipig by using mass spectrometry. In addition, sex-related differences in CYP protein abundance and correlation of CYP enzyme activity with CYP protein abundance were assessed. The following age groups were included: gestational day (GD) 84–86 (n = 8), GD 108 (n = 6), postnatal day (PND) 1 (n = 8), PND 3 (n = 8), PND 7 (n = 8), PND 28 (n = 8) and adult (n = 8). Liver microsomes were extracted and protein abundance was compared to that in adult animals. Next, the CYP protein abundance was correlated to CYP enzyme activity in the same biological samples. In general, CYP protein abundance gradually increased during development. However, we observed a stable protein expression over time for CYP4A24 and CYP20A1 and for CYP51A1, a high protein expression during the fetal stages was followed by a decrease during the first month of life and an increase toward adulthood. Sex-related differences were observed for CYP4V2_2a and CYP20A1 at PND 1 with highest expression in females for both isoforms. In the adult samples, sex-related differences were detected for CYP1A1, CYP1A2, CYP2A19, CYP2E1_2, CYP3A22, CYP4V2_2a and CYP4V2_2b with higher values in female compared to male Göttingen Minipigs. The correlation analysis between CYP protein abundance and CYP enzyme activity showed that CYP3A22 protein abundance correlated clearly with the metabolism of midazolam at PND 7. These data are remarkably comparable to human data and provide a valuable step forward in the construction of a neonatal and juvenile Göttingen Minipig PBPK model.

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Section: Sex-related Differences In Cyp Protein Abundance In the Developing Göttingen Minipigmentioning

confidence: 98%

Hepatic Cytochrome P450 Abundance and Activity in the Developing and Adult Göttingen Minipig: Pivotal Data for PBPK Modeling

et al. 2021

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mRNA Expression of CYP2E1, CYP2A19, CYP1A2, HSD3B, SULT1A1 and SULT2A1 genes in surgically castrated, immunologically castrated, entire male and female pigs and correlation with androstenone, skatole, indole and Improvac-specific antibody levels

Kubešová¹,

Šťastný²,

Faldyna³

et al. 2019

CZECH J ANIM SCI

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This study aimed to obtain a comprehensive look at the influence of castration on mRNA expression of the genes CYP2E1, CYP1A2, CYP2A19, HSD3B, SULT2A1 and SULT1A1 and their correlation with boar taint compounds (androstenone, skatole and indole) and Improvac-specific antibodies in a Czech commercial hybrid (Large White × Landrace (sow) × Duroc (boar)). Pigs were divided into groups of entire male pigs (NC), pigs castrated surgically (SC), pigs immunologically castrated and slaughtered 8 weeks (IM8) or 15 weeks (IM15) after the second dose of Improvac, and gilts (GI). Hepatic mRNA expression, measured by quantitative real-time polymerase chain reaction, differed significantly between the control group (entire male pigs) and all groups of interest for CYP2E1, CYP1A2 and CYP2A19. The mRNA level of the HSD3B gene differed significantly between the control group and the IM8, IM15 and GI groups. SULT1A1 gene expression was significantly different between the control group and the SC, IM8 and GI. In the case of SULT2A1, a significant difference was observed only between the control group and IM8 pigs. For all genes and treatment groups described above, expression was increased relative to the control. Significant differences for Improvac-specific antibodies between IM8 and IM15 groups were observed, indicating decrease of antibodies over time. Moreover, negative correlations between androstenone and mRNA levels of CYP2A19, CYP2E1 and SULT1A1 suggest that gene expression is suppressed.

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A correlation study of Boar taint-related genes, Boar tant substances and sex hormones in Bama miniature pigs at defferent ages

Cited by 2 publications

References 26 publications

Hepatic Cytochrome P450 Abundance and Activity in the Developing and Adult Göttingen Minipig: Pivotal Data for PBPK Modeling

Hepatic Cytochrome P450 Abundance and Activity in the Developing and Adult Göttingen Minipig: Pivotal Data for PBPK Modeling

mRNA Expression of CYP2E1, CYP2A19, CYP1A2, HSD3B, SULT1A1 and SULT2A1 genes in surgically castrated, immunologically castrated, entire male and female pigs and correlation with androstenone, skatole, indole and Improvac-specific antibody levels

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