Marcell T J, Harman S M, Urban R J, Metz D D, Rodgers B D, Blackman M R
Intramural Research Program, National Institute on Aging, National Institutes of Health, Maryland, USA.
Am J Physiol Endocrinol Metab. 2001 Dec;281(6):E1159-64. doi: 10.1152/ajpendo.2001.281.6.E1159.
Growth hormone (GH), insulin-like growth factor I (IGF-I), and testosterone (T) are important mediators of muscle protein synthesis, and thus muscle mass, all of which decline with age. We hypothesized that circulating hormones would be related to the transcriptional levels of their respective receptors and that this expression would be negatively related to expression of the myostatin gene. We therefore determined content of mRNA transcripts (by RT-PCR) for GH receptor (GHR), IGF-I, androgen receptor (AR), and myostatin in skeletal muscle biopsy samples from 27 healthy men >65 yr of age. There were no significant relationships between age, lean body mass, or percent body fat and transcript levels of GHR, IGF-I, AR, or myostatin. Moreover, there were no significant correlations of serum GH, IGF-I, or T with their corresponding target mRNA levels (GHR, intramuscular IGF-I, or AR) in skeletal muscle. However, GHR was negatively correlated (r = -0.60, P = 0.001) with myostatin mRNA levels. The lack of apparent relationships of muscle transcripts with their respective ligands in healthy older adults suggests that age-related deficits in both GH and T may lead to an increase in myostatin expression and a disassociation in autocrine IGF-I effects on muscle protein synthesis, both of which could contribute to age-related sarcopenia.
生长激素(GH)、胰岛素样生长因子I(IGF-I)和睾酮(T)是肌肉蛋白质合成以及肌肉量的重要调节因子,而所有这些都会随着年龄增长而下降。我们推测循环激素与其各自受体的转录水平相关,且这种表达与肌肉生长抑制素基因的表达呈负相关。因此,我们测定了27名65岁以上健康男性骨骼肌活检样本中生长激素受体(GHR)、IGF-I、雄激素受体(AR)和肌肉生长抑制素的mRNA转录本含量(通过逆转录聚合酶链反应)。年龄、瘦体重或体脂百分比与GHR、IGF-I、AR或肌肉生长抑制素的转录水平之间均无显著相关性。此外,血清GH、IGF-I或T与骨骼肌中其相应的靶mRNA水平(GHR、肌肉内IGF-I或AR)之间也无显著相关性。然而,GHR与肌肉生长抑制素mRNA水平呈负相关(r = -0.60,P = 0.001)。健康老年人中肌肉转录本与其各自配体之间缺乏明显相关性,这表明GH和T与年龄相关的缺乏可能导致肌肉生长抑制素表达增加以及自分泌IGF-I对肌肉蛋白质合成的作用脱节,这两者都可能导致与年龄相关的肌肉减少症。