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      Effects of GHRP-2 and Cysteamine Administration on Growth Performance, Somatotropic Axis Hormone and Muscle Protein Deposition in Yaks ( Bos grunniens) with Growth Retardation

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          Abstract

          The objective of this study was to investigate the effects of growth hormone-releasing peptide-2 (GHRP-2) and cysteamine (CS) administration on growth performance in yaks with growth retardation and try to elucidate its regulatory mechanisms. Trial 1, thirty-six 1-year-old Qinghai high plateau yaks (body weight 38–83.2 kg) were randomly chosen for body weight and jugular blood samples collection. The relationship between body weight and serum GHRH ( P < 0.05, R = 0.45), GH ( P < 0.05, R = 0.47), IGF-1 ( P < 0.05, R = 0.62) was significantly correlated in yaks colonies with lighter body weights. Trial 2, fifteen 1-year-old Qinghai high plateau yaks with growth retardation (average body weight 54.8 ± 8.24 kg) were randomly selected and assigned to negative control group (NG), GHRP-2 injection group (GG) and cysteamine feeding group (CG), with 5 yaks per group. Another five 1-year-old Qinghai high plateau yaks with normal growth performance (average body weight 75.3 ± 2.43 kg) were selected as positive control group (PG). The average daily gain (ADG) of the GG and CG were significantly higher than those in the PG and NG ( P < 0.05). Both GHRP-2 and CS administration significantly enhanced the myofiber diameter and area of skeletal muscle ( P<0.05). GHRP-2 significantly enhanced the serum GH and IGF-1 levels ( P < 0.05), and up-regulated GHR, IGF-1 and IGF-1R mRNA expression in the liver and skeletal muscle ( P < 0.05), enhanced the mRNA expression of PI 3 K, AKt and mTOR in the skeletal muscle ( P<0.05). CS significantly reduced the serum SS levels and the hypothalamus SS mRNA expression ( P < 0.05), and enhanced GHR and IGF-1 mRNA expression in the liver ( P < 0.05), decreased the mRNA expression of muscle atrophy F-box ( Atrogin-1) and muscle ring finger 1 ( MuRF1) mRNA ( P < 0.05). Conclusions: Growth retardation in yaks was primarily due to somatotropic axis hormones secretion deficiency. Both GHRP-2 and CS administration can accelerate growth performance and GH, IGF-1 secretion in yaks with growth retardation. GHRP-2 enhanced muscle protein deposition mainly by up-regulated the protein synthesis pathways, whereas CS worked mainly by down-regulated the ubiquitin-proteasome pathway.

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          Most cited references39

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          Insulin-like growth factors and their binding proteins: biological actions.

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            A receptor in pituitary and hypothalamus that functions in growth hormone release.

            Small synthetic molecules termed growth hormone secretagogues (GHSs) act on the pituitary gland and the hypothalamus to stimulate and amplify pulsatile growth hormone (GH) release. A heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPC-R) of the pituitary and arcuate ventro-medial and infundibular hypothalamus of swine and humans was cloned and was shown to be the target of the GHSs. On the basis of its pharmacological and molecular characterization, this GPC-R defines a neuroendocrine pathway for the control of pulsatile GH release and supports the notion that the GHSs mimic an undiscovered hormone.
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              Skeletal muscle hypertrophy and atrophy signaling pathways.

              Skeletal muscle hypertrophy is defined as an increase in muscle mass, which in the adult animal comes as a result of an increase in the size, as opposed to the number, of pre-existing skeletal muscle fibers. The protein growth factor insulin-like growth factor 1 (IGF-1) has been demonstrated to be sufficient to induce skeletal muscle hypertrophy. Over the past few years, signaling pathways which are activated by IGF-1, and which are responsible for regulating protein synthesis pathways, have been defined. More recently, it has been show that IGF-1 can also block the transcriptional upregulation of key mediators of skeletal muscle atrophy, the ubiquitin-ligases MuRF1 and MAFbx (also called Atrogin-1). Further, it has been demonstrated recently that activation of the NF-kappaB transcription pathway, activated by cachectic factors such as TNFalpha, is sufficient to induce skeletal muscle atrophy, and this atrophy occurs in part via NF-kappaB-mediated upregulation of MuRF1. Further work has demonstrated a trigger for MAFbx expression upon treatment with TNFalpha--the p38 MAPK pathway. This review will focus on the recent progress in the understanding of molecular signalling, which governs skeletal muscle atrophy and hypertrophy, and the known instances of cross-regulation between the two systems.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                19 February 2016
                2016
                : 11
                : 2
                : e0149461
                Affiliations
                [1 ]Institute of Animal Nutrition, Sichuan Agricultural University, Key Laboratory of Low Carbon Culture and Safety Production in Cattle in Sichuan, Chengdu, Sichuan, P.R. China
                [2 ]College of Animal Science and Technology, State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing, P.R. China
                [3 ]Animal Husbandry and Veterinary Institute, Haibei, Qinghai, P.R. China
                [4 ]Ningxia Xiahua Muslim Food Co. Ltd., Zhongwei, Ningxia, P.R. China
                [5 ]Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, P.R. China
                University of Macau, MACAO
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: ZW BC. Performed the experiments: RH HW XY XJ YW SZ HJ XK. Analyzed the data: RH. Contributed reagents/materials/analysis tools: SB WZ QN. Wrote the paper: RH QP ZW HZ.

                Article
                PONE-D-15-38219
                10.1371/journal.pone.0149461
                4760683
                26894743
                3d19a8fb-d8ea-416e-87ef-432c5bd80356
                © 2016 Hu et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 23 September 2015
                : 31 January 2016
                Page count
                Figures: 5, Tables: 6, Pages: 19
                Funding
                This study was supported by China Agriculuture (Beef Cattle/Yak) Research System (CARS-38) ( http://www.beefsys.com/) and Efficiently Special Key Technologies of Converting Grass to Livestock in Qinghai-Tibet Plateau Community (201203008). ZW received the funding. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Pediatrics
                Child Development
                Child Growth
                Growth Restriction
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Medicine and Health Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Biology and Life Sciences
                Anatomy
                Musculoskeletal System
                Muscles
                Skeletal Muscles
                Medicine and Health Sciences
                Anatomy
                Musculoskeletal System
                Muscles
                Skeletal Muscles
                Biology and Life Sciences
                Biochemistry
                Proteins
                Muscle Proteins
                Social Sciences
                Economics
                Resource Management (Economics)
                Rations
                Biology and Life Sciences
                Biochemistry
                Hormones
                Biology and Life Sciences
                Genetics
                Gene Expression
                Biology and Life Sciences
                Physiology
                Physiological Processes
                Secretion
                Medicine and Health Sciences
                Physiology
                Physiological Processes
                Secretion
                Custom metadata
                All relevant data are within the paper. All DNA primer are available from the NCBI database (accession numbers were listed in the article).

                Uncategorized
                Uncategorized

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