Abstract：
The growth hormone (GH)-insulin-like growth factor-1 (IGF-1) system regulates skeletal muscle growth and function. GH has a major function of targeting the liver to regulate IGF-1 production and release, and IGF-1 mediates the primary anabolic action of GH on growth. However, skeletal muscle is a target tissue of GH as evidenced by dynamic GH receptor expression, but it is unclear if GH elicits any direct actions on extrahepatic tissues as it is difficult to distinguish the effects of IGF-1 from GH. Fish growth regulation is complex compared to mammals, as genome duplication events have resulted in multiple isoforms of GHs, GHRs, IGFs, and IGFRs expressed in most fish tissues. This study investigated the potential for GH direct actions on fish skeletal muscle using an in vitro system, where rainbow trout myogenic precursor cells (MPCs) were cultured in normal and serum-deprived media, to mimic in vivo fasting conditions. Fasting reduces IGF-1 signaling in the muscle, which is critical for disentangling the roles of GH from IGF-1. The direct effects of GH were analyzed by measuring changes in myogenic proliferation and differentiation genes, as well as genes regulating muscle growth and proteolysis. This study provides the first in-depth analysis of the direct actions of GH on serum-deprived fish muscle cells in vitro. Data suggest that GH induces the expression of markers for proliferation and muscle growth in the presence of serum, but all observed GH action was blocked in serum-deprived conditions. Additionally, serum deprivation alone reduced the expression of several proliferation and differentiation markers, while increasing growth and proteolysis markers. Results also demonstrate dynamic gene expression response in the presence of GH and a JAK inhibitor in serum-provided but not serum-deprived conditions. These data provide a better understanding of GH signaling in relation to serum in trout muscle cells in vitro.
摘要：
生长激素（GH）-胰岛素样生长因子-1（IGF-1）系统调节骨骼肌的生长和功能。GH具有靶向肝脏调节IGF-1产生和释放的主要功能，IGF-1介导GH对生长的主要合成代谢作用。然而,骨骼肌是GH的靶组织，通过动态GH受体表达证明，但尚不清楚GH是否会对肝外组织产生直接作用，因为很难区分IGF-1和GH的作用。与哺乳动物相比，鱼类的生长调节是复杂的，由于基因组复制事件导致了GHs的多个亚型，GHRs,IGFs,和在大多数鱼类组织中表达的IGFR。这项研究调查了使用体外系统对鱼骨骼肌的GH直接作用的潜力，在正常和缺乏血清的培养基中培养虹鳟鱼生肌前体细胞（MPCs），模拟体内禁食条件。禁食会减少肌肉中的IGF-1信号传导，这对于从IGF-1中解开GH的作用至关重要。通过测量生肌增殖和分化基因的变化来分析GH的直接作用。以及调节肌肉生长和蛋白水解的基因。这项研究首次深入分析了GH对体外血清剥夺鱼肌肉细胞的直接作用。数据表明，GH在血清存在下诱导增殖和肌肉生长标志物的表达，但在血清剥夺条件下，所有观察到的GH作用均被阻断。此外,单独的血清剥夺减少了几种增殖和分化标志物的表达，同时增加生长和蛋白水解标记。结果还证明了在血清提供但非血清剥夺的条件下,在GH和JAK抑制剂存在下的动态基因表达应答。这些数据提供了对体外鳟鱼肌细胞中与血清相关的GH信号传导的更好理解。
