Hemmings K M, Daniel Z C T R, Buttery P J, Parr T, Brameld J M
School of Biosciences,Division of Nutritional Sciences,The University of Nottingham,Sutton Bonington Campus,Leicestershire,LE12 5RD,UK.
Animal. 2015 Feb;9(2):285-94. doi: 10.1017/S175173111400233X. Epub 2014 Sep 12.
Growth hormone (GH) and β agonists increase muscle mass, but the mechanisms for this response are unclear and the magnitude of response is thought to vary with age of animal. To investigate the mechanisms driving the muscle response to these agents, we examined the effects of short-term (6 day) administration of GH or cimaterol (a β2-adrenergic agonist, BA) on skeletal muscle phenotype in both young (day 60) and mature (day 120) lambs. Expression of myosin heavy chain (MyHC) isoforms were measured in Longissimus dorsi (LD), Semitendinosus (ST) and Supraspinatus (SS) muscles as markers of fibre type and metabolic enzyme activities were measured in LD. To investigate potential mechanisms regulating the changes in fibre type/metabolism, expression or activity of a number of signalling molecules were examined in LD. There were no effects of GH administration on MyHC isoform expression at either the mRNA or protein level in any of the muscles. However, BA treatment induced a proportional change in MyHC mRNA expression at both ages, with the %MyHCI and/or IIA mRNA being significantly decreased in all three muscles and %MyHCIIX/IIB mRNA significantly increased in the LD and ST. BA treatment induced de novo expression of MyHCIIB mRNA in LD, the fastest isoform not normally expressed in sheep LD, as well as increasing expression in the other two muscles. In the LD, the increased expression of the fastest MyHC isoforms (IIX and IIB) was associated with a decrease in isocitrate dehydrogenase activity, but no change in lactate dehydrogenase activity, indicating a reduced capacity for oxidative metabolism. In both young and mature lambs, changes in expression of metabolic regulatory factors were observed that might induce these changes in muscle metabolism/fibre type. In particular, BA treatment decreased PPAR-γ coactivator-1β mRNA and increased receptor-interacting protein 140 mRNA. The results suggest that the two agents work via different mechanisms or over different timescales, with only BA inducing changes in muscle mass and transitions to a faster, less oxidative fibre type after a 6-day treatment.
生长激素（GH）和β激动剂可增加肌肉量，但这种反应的机制尚不清楚，且人们认为反应程度会因动物年龄而异。为了研究驱动肌肉对这些药物产生反应的机制，我们检测了短期（6天）给予GH或西马特罗（一种β2 - 肾上腺素能激动剂，BA）对幼龄（60日龄）和成年（120日龄）羔羊骨骼肌表型的影响。在背最长肌（LD）、半腱肌（ST）和冈上肌（SS）中测量肌球蛋白重链（MyHC）亚型的表达，作为纤维类型的标志物，并在LD中测量代谢酶活性。为了研究调节纤维类型/代谢变化的潜在机制，检测了LD中一些信号分子的表达或活性。在任何肌肉中，给予GH对MyHC亚型在mRNA或蛋白质水平的表达均无影响。然而，BA处理在两个年龄段均诱导了MyHC mRNA表达的比例变化，所有三块肌肉中MyHCI和/或IIA mRNA的百分比显著降低，而LD和ST中MyHCIIX/IIB mRNA的百分比显著增加。BA处理诱导LD中MyHCIIB mRNA的从头表达，这是一种通常不在绵羊LD中表达的最快亚型，同时也增加了其他两块肌肉中的表达。在LD中，最快的MyHC亚型（IIX和IIB）表达增加与异柠檬酸脱氢酶活性降低相关，但乳酸脱氢酶活性无变化，表明氧化代谢能力降低。在幼龄和成年羔羊中，均观察到代谢调节因子表达的变化，这些变化可能诱导肌肉代谢/纤维类型的这些改变。特别是，BA处理降低了PPAR - γ共激活因子-1β mRNA并增加了受体相互作用蛋白140 mRNA。结果表明，这两种药物通过不同机制或在不同时间尺度上起作用，只有BA在6天治疗后诱导肌肉量变化并转变为更快、氧化程度更低的纤维类型。
