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  • irak pathway br Introduction The growth hormone secretagogue


    Introduction The growth hormone secretagogue receptor (GHSR) gene, which was first isolated from rats and humans (Kojima et al., 1999), comprises two exons and one intron in mammals and chicken. The pig GHSR is located on chromosome 13 (range 110,981,465–111,006,149 on Reference Sscrofa11.1). Alternative splicing of the transcribed GHSR RNA generates two protein isoforms, GHSR1a and GHSR1b. The functionally active form of GHSR, called GHSR1a, is a seven-transmembrane domain receptor that is expressed in multiple tissues, including the pituitary gland, kidney, thymus, pancreas, myocardium, and adipose (Abizaid et al., 2006, Dixit et al., 2007, Venables et al., 2011). In addition, the expression of ghrelin and GHSR1a has been detected in reproductive tissues, including the uterus (Unsal and Sönmez, 2013) and ovary (Gupta et al., 2015). The GHSR protein binds to ghrelin to play a critical role in the central and peripheral regulation of growth hormone secretagogues, appetite stimulation, food intake, irak pathway homeostasis, lipogenesis, suppression of brown fat thermogenesis, and improvement of cardiovascular functions (Schellekens et al., 2010, Yin et al., 2014, Müller et al., 2015, Yuan et al., 2016). Naturally occurring mutations of GHSR are associated with growth disorders, metabolic syndromes, and obesity in humans (Baessler et al., 2005, Liu et al., 2007, Mager et al., 2008, Inoue et al., 2011). GHSR has been identified as a potential candidate gene in quantitative trait locus and half-sib regression analyses of growth traits in Japanese black cattle (Malau-Aduli et al., 2005). In chicken, four single nucleotide polymorphisms (SNPs) in GHSR are associated with growth and carcass traits (Fang et al., 2010); other SNPs are significantly associated with fat deposition and muscle fiber traits (Lei et al., 2007). An association between a ghrelin gene polymorphism and chicken growth has also been established (Li et al., 2006, Fang et al., 2007). In cattle, two GHSR gene mutations have been shown to have a significant effect on body weight in Nanyang cattle (Zhang et al., 2009). In light of the information available from various species, we suggest that GHSR might be a candidate gene for growth traits in pigs. Therefore, the aim of this study was to investigate differences in GHSR1a levels among different pig strains and to identify SNPs that could be used to analyze the association of GHSR with growth traits in pigs. The identification of such SNPs could provide molecular markers for use in marker-assisted selection of pigs.
    Materials and methods
    Discussion As a target of the endogenous ligand ghrelin, GHSR integrates two anabolic actions: first, it mediates the stimulatory effect of ghrelin on growth hormone (GH) release; and second, it communicates the orexigenic and adipogenic activities of ghrelin, thereby contributing to energy balance (Müller et al., 2015). GH can influence the growth of peripheral organs (Baessler et al., 2006). The pathway activated by GHSR regulates the activation of the downstream mitogen-activated protein kinase (Akt), nitric oxide synthase, and AMP-activated protein kinase (AMPK) cascades in different cellular systems (Yin et al., 2014). This activity seems to provide the tonic signal required for the development of normal height, probably through an effect on the GH axis (Pantel et al., 2006). Some polymorphisms of the GHSR gene were reported to be associated with human diseases or abnormal phenotypes and growth performance. In humans, a transversion mutation generates a critical change in the GHSR-associated constitutive activity and results in an unusual pathogenic mechanism of growth failure (Pantel et al., 2006). In this study, no SNPs were found in the coding region of the pig GHSR gene, suggesting that the constitutive composition of the GHSR gene was conserved among the pig breeds, and the regulative function of this gene was possibly mediated through variations in expression levels. A SNP in the 5′-flanking region of the GHSR gene was found to be associated with body weight (Mager et al., 2008). In our study, the SNP C-1595A, which is located 1595bp upstream from the 5′-flanking region of the GHSR gene, varied among the four pig breeds, and the C-allele of this SNP was found at a higher frequency in fast-growing Yorkshire pigs than in slower-growing Chinese breeds (Tibetan and Diannan small-eared pigs). These results are consistent with our finding of a SNP in the 5′-flanking region of the GHSR gene. In addition, we found that the growth rate of New Huai pigs with a CC genotype was significantly higher than that of the animals with AC and AA genotypes. The results suggest that the C-allele of GHSR C-1595A might be advantageous for a higher growth rate in pigs, and that it could be used as a DNA marker for pig breeding.