title: Effects of nuclear receptor transactivation on boar taint metabolism and gene expression in porcine hepatocytes.
abstract: The accumulation of the testicular steroid androstenone (AND) and tryptophan degradation product skatole (3MI) in fat results in boar taint, an off odor and flavor in boar meat. Increasing boar taint metabolism in the liver may help limit the deposition of AND and 3MI in fat, thereby improving meat quality. The effects of transactivation of the nuclear receptors constitutive androstane receptor (CAR), pregnane X receptor (PXR), and farnesoid X receptor (FXR) on the expression levels of several transcripts of interest and the metabolism of AND and 3MI in primary porcine hepatocytes were tested. Primary cells were isolated from mature boars, and transcript expression levels were assayed using real-time PCR. The transcripts of interest included porcine orthologs of common phase I and phase II metabolic enzymes and transcripts previously shown to be differentially expressed in boars with high boar taint levels. Transactivation of CAR, PXR, or FXR resulted in altered expression of several transcripts, including increased expression of cytochrome P450 (CYP) 2B22 by CAR, of CYP2A19, CYP2B22, CYP2C33, and CYP2C49 by PXR, of CYP2C33 and CYP2E1 by FXR, and of CYP19A2 by all three receptors. Only transactivation of PXR had a significant effect on AND metabolism, resulting in 7.5±1.5% of the initial level of AND remaining compared to 21.4±3.1% remaining with control dimethyl sulfoxide (DMSO) treatment. FXR had the greatest effect on 3MI metabolism, increasing the expression of CYP2E1 by 1.29-fold and increasing the production of the key metabolite 6-hydroxy-3-methylindole (6-OH-3MI), while decreasing 5-hydroxy-3-methylindole (5-OH-3MI) production. 3-Hydroxy-3-methyloxindole (HMOI) production was increased by CAR transactivation, while indol-3-carbinol (I3C) production was increased by PXR and FXR transactivation, and by treatment with 5β-dihydrotestosterone (5β-DHT). From this, it can be concluded that selective transactivation of PXR and FXR may be a viable means of decreasing boar taint by increasing the hepatic metabolism of AND and 3MI.
authors.affiliation: Department of Animal and Poultry Science, University of Guelph, Guelph, Ontario, Canada N1G2W1.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Gray
authors.forename: E James
authors.initials: EJ
authors.lastname: Squires
mesh_terms: D000738:Androsterone / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D000090702:Constitutive Androstane Receptor; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D013196:Dihydrotestosterone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D015870:Gene Expression; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009812:Odorants; D000077297:Pregnane X Receptor; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D011987:Receptors, Steroid / Q000235:genetics; D012293:Rifampin / Q000494:pharmacology; D012862:Skatole / Q000378:metabolism; D034421:Sus scrofa; D015533:Transcriptional Activation; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D000738:Androsterone; D002635:Chenodeoxycholic Acid; D000090702:Constitutive Androstane Receptor; D003577:Cytochrome P-450 Enzyme System; D013196:Dihydrotestosterone; D004958:Estradiol; D000077297:Pregnane X Receptor; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D012293:Rifampin; D012862:Skatole; D000099150:Receptor, Farnesoid X-Activated