Androgen-mediated down-regulation of CYP1A subfamily genes in the pig liver

Abstract

In Meishan and Landrace pigs, sex differences in the constitutive expression of hepatic cytochrome P4501A (CYP1A) subfamily enzymes were examined in terms of their mRNA, protein, and enzyme activity. All the results from the real-time RT-PCR, western blotting, and enzyme assays for CYP1A subfamily enzymes indicated that, in 5-month-old Meishan pigs, the expression levels of CYP1A1 and CYP1A2 in males were significantly low as compared with those in females. In contrast, there were no such significant sex differences in Landrace pigs. Castration of male Meishan pigs led to a female-type expression of the CYP1A subfamily enzymes, whereas no such effect was observed in male Landrace pigs after castration. In both breeds of pigs, the administration of testosterone propionate to the females and castrated males led to marked decreases in the expression levels of mRNAs and proteins in the CYP1A subfamily enzymes, and also in their enzyme activities. Furthermore, the correlation analyses between the serum testosterone level and the gene expression levels of CYP1A subfamily enzymes in different sex-matured (1-5-month-old) male pigs revealed that the clear decrease in expression levels of hepatic CYP1A subfamily enzymes occurred at concentrations of more than 33 ng/ml of serum testosterone. Incidentally, the mean concentrations of serum testosterone in 5-month-old Landrace and Meishan pigs were around 18 and 50 ng/ml respectively. In conclusion, we demonstrated for the first time that the serum testosterone level is one of the physiological factors which regulate constitutive expression of hepatic CYP1A1 and CYP1A2 in pigs.

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

“…However, androstenone alone did not affect CYP2E1 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].…”

In vitro inhibition of porcine cytochrome P450 by 17β-estradiol and 17α-estradiol

“…The interest in porcine CYP450 is increasing because pigs can be used as an animal model in pharmacological and toxicological investigations of new drugs and chemical compounds. It is well known that testicular steroids affect porcine CYP450 activity either directly (Zamaratskaia et al ., 2007; Rasmussen et al ., 2010, Rasmussen et al ., 2011a) or by affecting CYP gene/protein expression (Doran et al ., 2002; Tambyrajah et al ., 2004; Gillberg et al ., 2006; Kojima et al ., 2010). This in turn can modify the presence of foreign compounds or the magnitude by which they are metabolised.…”

Estrus synchronization in microminipig using estradiol dipropionate and prostaglandin F_2α

“…Cytochrome P450 enzymes (CYP1A and CYP2E) and 3β-hydoroxysteroid dehydrogenase are reported to be involved in the metabolism of testicular steroids (androstenone, estradiol-17β, and testosterone) in domestic pigs [39,40,41]. However, mRNA expressions and activities of steroid metabolizing enzymes in the porcine liver after testicular steroid treatment are known to vary with age [42], breed [42] and gender [40, 42]. From these reports, it was surmised that the enzymes and activities involved in steroid metabolism in the liver may differ between domestic pigs and MMpigs.…”