Inhibitory effects of the beta-adrenergic receptor agonist zilpaterol on the LPS-induced production of TNF-alpha in vitro and in vivo

In this study the anti-inflammatory properties of zilpaterol, a beta2-adrenergic receptor (AR) agonist specifically developed as a growth promoter in cattle were investigated. Although zilpaterol has a different structure compared with the beta2-AR agonists known to date, it was noted that it was able to bind to both the beta2-AR (Ki = 1.1 x 10(-6)) and the beta1-AR (Ki = 1.0 x 10(-5)). Using lipopolysaccharide (LPS)-exposed U937 macrophages, the production of cyclic adenosine-3',5'-cyclic monophosphate (cAMP) and tumor necrosis factor alpha (TNF-alpha) were investigated. Zilpaterol inhibited TNF-alpha release and induced intracellular cAMP levels in a dose-dependent manner. The inhibition of TNF-alpha release and induction of cAMP production was mainly mediated via the beta2-AR, as indicated by addition of beta1- and beta2-specific antagonists. The effects of zilpaterol were investigated in LPS-treated male Wistar rats after pretreatment with zilpaterol. Zilpaterol dosed at 500 microg/kg body weight reduced the TNF-alpha plasma levels. In conclusion, zilpaterol is a beta2-adrenergic agonist and an inhibitor of TNF-alpha production induced by LPS both in vivo and in vitro.     

Selection for growth rate or against back fat thickness in pigs is associated with changes in growth hormone axis plasma protein concentration and mRNA level.

Selection for increased growth rate or decreased back fat thickness results in concomitant changes in endocrine and metabolic status. Growth hormone (GH) changes in blood plasma concentration related to selection for growth rate and fat deposition were reported in pigs. The molecular mechanisms regulating selection-induced changes in GH plasma concentration remain largely unknown. We investigated selection-associated changes in GH axis parameters in 2 pig lines selected for increased growth rate (F-line), or decreased back fat thickness (L-line), respectively. First, we investigated selection-associated changes in GH pulse parameters. In both selection lines we found each generation a declining GH peak maximum concentration and area under the GH curve. GH pulse width was not associated with generation number. In both lines generation number was associated with a declined pulse interval, indicating that the number of pulses per day increased on average with 1 pulse per 24 h per generation. Second, plasma concentration of GH axis related Insulin-like growth factor-I (IGF-I) and insulin were investigated. Plasma IGF-I concentration was not associated with generation number in the F-line. Mean plasma insulin concentration declined each generation in both lines. Third, we investigated changes in GH and Pit-1 mRNA levels. In both selection lines GH and Pit-1 mRNA levels increased approximately 50% each generation. The high SD of the GH mRNA levels in both lines may suggest that the GH mRNA levels are pulsatile in vivo. We postulate a molecular mechanism that may explain how selection is associated with increased GH mRNA levels and GH pulse numbers, while lowering GH release per pulse.     

Disease-induced variability of genetic correlations: ascites in broilers as a case study

Breeding against a production disease is complicated by multiple relationships between productivity, disease, and environment. Ascites in broilers is such a disease. The combination of the reasonably well understood etiology (a physiological/pathological cascade due to inadequate oxygen supply) and the practical relevance makes ascites a relevant case for demonstrating and partly revealing these complex relationships. Chickens (n = 2,788) were tested in an ascites-challenging (cold) environment. Genetic analysis of mortality and pathology in combination with performance and physiological traits (especially blood gas traits) revealed ample opportunities for selection against ascites expression. The genetic correlation structure indicated that different mortality traits and pathology traits roughly represent one common characteristic. Direct selection against pathology is more effective than selection on the basis of growth or blood gas traits. The observed negative correlation (-0.26) between productivity and ascites was unexpected. From the etiology of ascites (inadequate supply of oxygen relative to the demand), a positive (unfavorable) correlation was expected. To demonstrate that the actual disease occurrence caused this apparent contradiction, the data from the undiseased subpopulation were reanalyzed. In the undiseased subpopulation, the genetic correlation between productivity and ascites was positive (0.29). This discrepancy was confirmed by comparing regression of ascites expression on actual performance with regression of ascites on independently assessed performance breeding values. The lability of the genetic correlation was explained from complex interactions between productivity, disease susceptibility, and actual occurrence of the disease. The revealed mechanism can be generalized to other production-related diseases and results in systematically lower genetic correlations between disease and productivity. It was inferred that genetic correlations between productivity and such diseases will always be prone to the demonstrated environmental sensitivity, which complicates index selection against production-related diseases.     

Molecular genetic and physiologic background of the growth hormone-IGF-I axis in relation to breeding for growth rate and leanness in pigs

The GH-IGF-I axis is of major importance for the regulation of body growth and composition, and cellular proliferation and differentiation processes. Selective breeding aiming to improve growth rate and/or body composition is accompanied by changes of the GH-IGF-I axis. Research aiming to elucidate the genetic and physiologic mechanism(s) underlying these changes may best use single-trait selection lines. Two such pig selection lines, one for growth rate and one for high lean content, were used in experiments to investigate the mechanisms of the GH-IGF-I axis change during selection. This contribution reviews the selection-related changes in the GH-IGF-I axis as the consequences of selection for whole body growth rate or body composition and effects on local tissue growth rate. A model explaining the observed effects and consequences for the pressure on the physiology is presented. In short, selection related demand for GH induces GH synthesis until a limit is reached. After that the pulsatile GH plasma profile changes, which may also affect expression profiles of genes regulating body composition.     

Genetic diversity of European Miscanthus species revealed by AFLP fingerprinting

The genetic diversity of European species of Miscanthus was analyzed by AFLP technique. The genetic similarity based on six primer combinations yielded about 200 data points. The plant material included 11 clones of M. sinensis, 2 clones of M. sacchariflorus and 31 accessions of M. x giganteus. Furthermore 4 hybrids were created by crossing M. sinensis with M. sacchariflorus clones. Two clusters were found represented by M. sinensis and M. sacchariflorus clones. The M. x giganteus accessions clustered under M. sacchariflorus. A very low genetic diversity was found in the M. x giganteus pool. No polymorphism was detected between micro- and rhizome-propagated M. x giganteus accessions. Many of the M. sacchariflorus clones sampled in Botanical Gardens turned out to be M. x giganteus clones. In the hybridization of M. sinensis and M. sacchariflorus material, self-fertilization of the M. sinensis clones was determined by application of the AFLP technique. In the M. sinensis pool a typical diversification of hybrids was detected according to ornamental selection by horticulture breeders. The AFLP technique is an adequate and powerful tool to evaluate genetic diversification, to analyse the success of hybridizations and to find wrong classifications.     

Breeding for societally important traits in pigs

Pig breeding programs traditionally focus on the genetic improvement of production and reproduction traits that have a clear economic value. Because citizens and consumers increasingly attach value to traits that have little or no direct relationship to production costs or to the price of a product, pig breeding organizations want to pay more attention to societally important traits, such as the welfare and health of pigs, the ecological effects of pork production, and the healthiness and sensory quality of pork. Most societally important traits have an economic and a noneconomic value and are sufficiently heritable for effective genetic selection, although many genetic and phenotypic (co)-variances still have to be estimated. However, it often is not clear to a pig breeding organization how it may deal with the noneconomic value of breeding-goal traits. In this study, a retrospective selection-index method is proposed to obtain the proper weights for societally important traits in the breeding goal. First, the genetic-progress space for each breeding-goal trait is explored by increasing the weights, in a stepwise manner, to each societally important trait in the breeding goal, starting from zero. Subsequently, a pig breeding organization can adopt the resulting genetic-progress scenario that it considers most sustainable or most acceptable. The weights underlying the adopted scenario are considered to be the proper breeding-goal weights. The noneconomic value of each societally important breeding-goal trait is found by deducting its economic value from its obtained weight and is thereby expressed in monetary units. In addition to obtaining weights for societally important breeding-goal traits, the proposed method offers the possibility to estimate the societal costs of selecting for economic traits only, as well as the societal benefits and the economic costs of selecting for traits with a noneconomic value. The method is therefore a useful tool for the development of sustainable breeding goals. An example has been worked out for a sow-line breeding program.