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Pork odour is to a great extent affected by the presence of malodorous compounds, mainly androstenone and skatole. The present review outlines the current state of knowledge about factors involved in the regulation of androstenone and skatole in entire male pigs. Androstenone is a pheromonal steroid synthesised in the testes and metabolised in the liver. Part of androstenone accumulates in adipose tissue causing a urine-like odour. Skatole is produced in the large intestine by bacterial degradation of tryptophan and metabolised by hepatic cytochrome P450 enzymes and sulphotransferase. The un-metabolised part accumulates in adipose tissue, causing faecal-like odour. Androstenone levels are mostly determined by genetic factors and stage of puberty, whereas skatole levels in addition to genetic background and hormonal status of the pigs are also controlled by nutritional and environmental factors. To reduce the risk of tainted carcasses entering the market, male pigs are surgically castrated in many countries. However, entire males compared to castrates have superior production characteristics: higher growth rate, better feed efficiency and leaner carcasses. Additionally, animal welfare aspects are currently of particular importance in light of increasing consumers' concerns. Nutrition, hormonal status, genetic influence on boar taint compounds and the methods to develop genetic markers are discussed. Boar taint due to high levels of skatole and androstenone is moderately heritable and not all market weight entire males have boar taint; it should thus be possible to select for pigs that do not have boar taint. In these studies, it is critical to assess the steroidogenic potential of the pigs in order to separate late-maturing pigs from those with a low genetic potential for boar taint. A number of candidate genes for boar taint have been identified and work is continuing to develop genetic markers for low boar taint. More research is needed to clarify the factors involved in the development of boar taint and to develop additional methods to prevent the accumulation of high concentrations of skatole and androstenone in fat. This review proposes those areas requiring further research.

The pregnane X receptor (PXR) plays an important role in the response to xenobiotics and endogenous toxins. We have used a specific anti-PXR antibody in the Western blotting of mouse liver nuclear extracts to show that PXR is accumulated in the nucleus after treatment with 5-pregnen-3␤-ol-20-one-16␣-carbonitrile (PCN), followed by an increase in Cyp3a11 mRNA. Expression of wild type PXR and various mutants as green fluorescent fusion proteins in mouse livers showed that PXR was retained in the cytoplasm from where PCN treatment translocated PXR into the nucleus. Furthermore, the xenochemical response signal, the nuclear translocation signal, and the activation function 2 domain were all required for the nuclear translocation to occur. Immunoprecipitation experiments using the hsp90 antibody demonstrated the presence of PXR in a complex with the endogenous cytoplasmic constitutive active/androstane receptor retention protein (CCRP) in HepG2 cells. Fluorescence resonance energy transfer analysis of mouse liver sections after co-expression of cyan fluorescent protein-CCRP and yellow fluorescent protein-PXR also indicated that CCRP and PXR were closely associated in vivo. Overexpression of exogenous CCRP increased the cytoplasmic level of the PXR⅐CCRP⅐hsp90 complex, whereas a decrease in endogenous CCRP by treatment with small interfering RNA for CCRP repressed the PXR-mediated reporter activity in HepG2 cells. We conclude that the CCRP mediates the retention of PXR in the cytosol and modulates the activation of PXR in response to PCN treatment.The pregnane X receptor (PXR, 1 NR1I2) and constitutive active/androstane receptor (CAR, NR1I3) are involved in the primary response to xenobiotics and endogenous toxins (1, 2).These receptors respond to ligands by activating the expression of genes encoding enzymes involved in phase I (oxidation) and phase II (conjugation) metabolism as well as proteins involved in the efflux of toxins from the cell (3-5). CAR is normally sequestered in the cytoplasm of untreated liver cells and translocates to the nucleus after exposure to PB and PB-like chemicals (6). The cytoplasmic CAR retention protein (CCRP and designated Dnajc7 in the official gene symbol in the NCBI data base) has been shown to maintain the cytoplasmic localization of CAR by forming a complex with CAR and hsp90 (7, 8). Other nuclear receptors, such as the glucocorticoid receptor (GR), vitamin D receptor (VDR), and aryl hydrocarbon receptor also exist as complexes with receptor-specific co-chaperones and hsp90 that play an important role in locating these receptors in the cytoplasm of unstimulated cells (9). These co-chaperones, including immunophilin-FK506-binding proteins and hepatitis B virus protein X-associated protein 2, contain multiple tetratricopeptide repeat (TPR) motifs, which are 34 amino acid sequences that form a pair of anti-parallel ␣ helices that mediate protein-protein interactions and the assembly of multiprotein complexes (10).The movement of proteins between the nucleus and the cytoplasm is an ene...

The co-occurrence of Fusarium mycotoxins in contaminated swine diets has been shown to result in synergistic toxicity beyond that observed for individual toxins. An experiment was conducted, therefore, to investigate the effects of feeding a blend of grains naturally contaminated with Fusarium mycotoxins on growth, brain regional neurochemistry, serum immunoglobulin (Ig) concentrations, serum chemistry, hematology, and organ weights of starter pigs. Three levels of glucomannan polymer (GM polymer, extract of yeast cell wall, Alltech Inc.) were also tested for its efficacy to overcome Fusarium mycotoxicoses. A total of 175 starter pigs (initial weight of 10 +/- 1.1 kg) were fed five diets (seven pens of five pigs per diet) for 21 d. Diets included (1) control, (2) blend of contaminated grains, (3) contaminated grains + 0.05% GM polymer (4) contaminated grains + 0.10% GM polymer and (5) contaminated grains + 0.20% GM polymer. Diets containing contaminated grains averaged 5.5 ppm deoxynivalenol, 0.5 ppm 15-acetyldeoxynivalenol, 26.8 ppm fuuric acid, and 0.4 ppm zearalenone. Feed intake and weight gain of all pigs fed contaminated grains was significantly reduced compared to controls throughout the experiment. The weights of liver and kidney, expressed as a percentage of body weight, were lower in pigs fed the contaminated diet than in those fed the control diet. The feeding of contaminated grains significantly reduced concentrations of dopamine in the hypothalamus and pons and concentrations of dihydroxyphenylacetic acid and norepinephrine in the pons. The ratios of 5-hydroxyindoleacetic acid to serotonin, however, were elevated in the hypothalamus and pons. The feeding of contaminated grains increased serum IgM and IgA concentrations, while serum IgG concentrations were not altered. The supplementation of GM polymer prevented some of the mycotoxin-induced alterations in brain neurotransmitter and serum Ig concentrations. In summary, the feeding of grains naturally contaminated with Fusarium mycotoxins reduced growth, altered brain neurochemistry, increased serum Ig concentrations, and decreased organ weights in starter pigs. Some of the Fusarium mycotoxin-induced changes in neurochemistry and serum Ig concentrations can be prevented by the feeding of yeast cell wall polymer at appropriate concentrations, although this was not reflected in increased growth rate under these experimental conditions.

Cholestatic liver disease is one of the most common metabolic problems associated with total parenteral nutrition (TPN) in preterm infants, and it is strongly related to the duration of TPN ( 1 ). The incidence of parenteral nutrition-associated liver disease (PNALD) in infants who Abstract Total parenteral nutrition (TPN) is associated with the development of parenteral nutrition-associated liver disease (PNALD) in infants. Fish oil-based lipid emulsions can reverse PNALD, yet it is unknown if they can prevent PNALD. We studied preterm pigs administered TPN for 14 days with either 100% soybean oil (IL), 100% fi sh oil (OV), or a mixture of soybean oil, medium chain triglycerides (MCTs), olive oil, and fi sh oil (SL); a group was fed formula enterally (ENT). In TPN-fed pigs, serum direct bilirubin, gamma glutamyl transferase (GGT), and plasma bile acids increased after the 14 day treatment but were highest in IL pigs. All TPN pigs had suppressed hepatic expression of farnesoid X receptor (FXR), cholesterol 7-hydroxylase (CYP7A1), and plasma 7 ␣ -hydroxy-4-cholesten-3-one (C4) concentrations, yet hepatic CYP7A1 protein abundance was increased only in the IL versus ENT group. Organic solute transporter alpha (OST ␣ ) gene expression was the highest in the IL group and paralleled plasma bile acid levels. In cultured hepatocytes, bile acid-induced bile salt export pump (BSEP) expression was inhibited by phytosterol treatment. We show that TPN-fed pigs given soybean oil developed cholestasis and steatosis that was prevented with both This work was supported in part by federal funds from the USDA,, the American Society for Parenteral and Enteral Nutrition, Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BSEP, bile salt export pump; CA, cholic acid; CDCA, chenodeoxycholic acid; C4, 7 ␣ -hydroxy-4-cholesten-3-one; CYP8B1, sterol 12-alpha-hydroxylase; CYP7A1, cholesterol 7-hydroxylase; CYP3A29, cytochrome P450 3A29; CYP27A1, sterol 27-hydroxylase; FGF, fi broblast growth factor; FXR, farnesoid X receptor; GGT, gamma glutamyl transferase; MCT, medium chain triglyceride; MRP3, multidrug resistant protein 3; NTCP, Na + / taurocholate cotransporter; OBCA, obeticholic acid; OST ␣ / ␤ , organic solute transporters alpha and beta; PNALD, parenteral nutrition-associated liver disease; TPN, total parenteral nutrition; UDCA, ursodeoxycholic acid . and immediately placed in cages housed at 31°C to 32°C, as described previously ( 12 ). Based on body weight, pigs delivered from each sow were randomly assigned to one of the three TPN treatment groups or to enteral nutrition (ENT). After delivery, pigs were surgically implanted with catheters into the jugular vein and umbilical artery. Pigs in the enteral group also were implanted with an orogastric feeding tube, whereas TPN groups received a sham puncture. Maternal plasma (16 ml/kg intravenously during the fi rst 24 h) was administered for passive immunological protection. During the 14 day study, pigs received antibiotics (enrofl oxacin 5 mg/kg) intrave...

The objectives were to determine the duration of the stress response associated with cautery dehorning and to assess the effectiveness of the nonsteroidal anti-inflammatory drug meloxicam (Metacam, 20 mg/mL solution for injection) for reducing that response. Sixty Holstein heifer calves were blocked by age and randomly assigned to receive an i.m. injection of meloxicam or a placebo (0.5 mg/kg). All calves were given a lidocaine cornual nerve block delivered 5 mL per side 10 min before dehorning. To establish baseline values, calves were sham dehorned 24 h before actual dehorning. Blood samples were taken via indwelling jugular catheters at 0, 0.5, 1, 1.5, 2, 4, 6, and 24 h after the procedure. Heart and respiratory rates were also taken at these times. Data were analyzed using PROC MIXED in SAS. Analysis of covariance was employed to assess the difference between sham and dehorning at each time period. Dehorning was associated with elevated serum cortisol (d -1: 33.9 +/- 1.26; d 0: 46.2 +/- 2.33 nmol/L) and heart rate (d -1: 108 +/- 1.8; d 0: 109.4 +/- 2.4 beats per minute) in both groups for 24 h, and elevated respiratory rate (sham: 42.2 +/- 1.95 vs. dehorning: 45.1 +/- 2.19 respirations per minute) in both groups for 6 h. A treatment x time interaction was found for cortisol, with meloxicam calves having lower serum cortisol than controls until 6 h after dehorning (meloxicam: 49.7 +/- 4.37 vs. control: 63.0 +/- 6.94 nmol/L). There was no difference between the treatment groups at 24 h (meloxicam: 35.2 +/- 2.74 and control: 34.8 +/- 3.64 nmol/L of cortisol). Overall, the changes in heart rates (increase meloxicam: 3.74 +/- 0.96 vs. control: 4.70 +/- 1.87) and respiratory rates (increase meloxicam: 2 +/- 0.1 vs. control: 4 +/- 0.2) were greater in the control group compared with the meloxicam group. These results indicate that meloxicam reduced the physiological stress response to dehorning.

Introduction Parenteral nutrition (PN) in preterm infants leads to PN-associated liver disease (PNALD). PNALD has been linked to serum accumulation of phytosterols that are abundant in plant oil but absent in fish oil emulsions. Hypothesis Whether modifying the phytosterol and vitamin E composition of soy and fish oil lipid emulsions affects development of PNALD in preterm pigs. Methods We measured markers of PNALD in preterm pigs that received 14 days of PN that included 1 of the following: (1) Intralipid (IL, 100% soybean oil), (2) Intralipid + vitamin E (ILE, d-α-tocopherol), (3) Omegaven (OV, 100% fish oil), or (4) Omegaven + phytosterols (PS, β-sitosterol, campesterol, and stigmasterol). Results Serum levels of direct bilirubin, gamma glutamyl transferase, serum triglyceride, low-density lipoprotein, and hepatic triglyceride content were significantly lower (P < .05) in the ILE, OV, and PS compared to IL. Hepatic cholesterol 7-hydroxylase and organic solute transporter–α expression was lower (P < .05) and portal plasma FGF19 higher in the ILE, OV, and PS vs IL. Hepatic expression of mitochondrial carnitine palmitoyltransferase 1A and microsomal cytochrome P450 2E1 fatty acid oxidation genes was higher in ILE, OV, and PS vs IL. In vivo 13C-CDCA clearance and expression of pregnane X receptor target genes, cytochrome P450 3A29 and multidrug resistance-associated protein 2, were higher in ILE, OV, and PS vs IL. Conclusions α-tocopherol in Omegaven and added to Intralipid prevented serum and liver increases in biliary and lipidemic markers of PNALD in preterm piglets. The addition of phytosterols to Omegaven did not produce evidence of PNALD.

The effect of a newly developed anti-LH-RH vaccine on the performance, sexual development, and incidence of boar taint-related compounds was investigated in young intact male pigs. At 29 kg BW, 40 crossbred intact males and 20 castrates were allocated to three groups. Castrates and half of the intact males were untreated. The remaining intact males were immunized against LH-RH at 29 kg and again at 89 kg BW. All pigs were slaughtered at 105 kg BW. Compared with control intact males, feed efficiency in castrates was decreased by 10%, muscle content was reduced by 5%, and carcass fat content was increased by 26%. Growth performance and carcass traits did not differ significantly between immunized and control intact males. Genital tract weight, measured at slaughter, was decreased (P < or = .002) by immunization. Plasma testosterone concentrations were not significantly affected at 89 kg BW, whereas they were sevenfold lower (P < .001) in immunized than in control intact males at 105 kg BW. Fat androsterone levels, measured at slaughter, were substantially reduced (P < .001) from .66 +/- .07 microgram/g in control to .21 +/- .01 microgram/g in immunized intact males. Rates of testicular steroid biosynthesis, measured in vitro, were decreased by immunocastration. Fat skatole levels were very low and did not differ significantly between the three groups. The present results demonstrate that anti-LHRH immunization was effective in reducing the level of androstenone, a boar taint-related compound, although having a limited effect on the performance of the animals.