Objective

Traditional weight-based regimens of GH replacement are more effective at reversing the loss of skeletal muscle in GH-deficient adults than currently recommended regimens, where the dose of GH is increased to restore serum concentrations of IGF-1. While weight-based regimens increase concentrations of IGF-1 and decrease concentrations of myostatin, it is not known whether the reduced effectiveness of individually titrated GH regimens is due to ongoing hypersecretion of myostatin. Consequently, the aims of this study were to determine whether concentrations of myostatin in blood and skeletal muscle are increased in GH-deficient adults, and whether these concentrations are decreased by GH replacement regimens titrated to restore serum IGF-1.

Design

Twenty-six GH deficient adults (18 men and 8 women) were treated with individualised regimens of recombinant human GH aiming to achieve serum concentrations of IGF-1 within one standard deviation of the age- and gender-adjusted mean. Plasma concentrations of myostatin were measured at baseline and after 6 months of treatment were compared to fifteen healthy controls (9 men and 6 women). Skeletal muscle biopsies were performed in 19 of these GH-deficient adults (15 men and 4 women) and 10 of the healthy controls (6 men and 4 women). Expression of IGF-1 and myostatin mRNA was determined by qPCR.

Results

Concentrations of IGF-1 in serum and mRNA in skeletal muscle were reduced, and concentrations of myostatin in plasma and mRNA in skeletal muscle were increased in GH-deficient adults at baseline (P < .05 versus healthy controls). Despite restoring concentrations of IGF-1, GH replacement did not reduce concentrations of myostatin in either blood or skeletal muscle. Concentrations of IGF-1 and myostatin in both blood and skeletal muscle were positively correlated in GH-deficient adults at baseline (P < .05), but not in GH-replete adults.

Conclusions

Concentrations of myostatin in blood and skeletal muscle are increased in GH-deficient adults. Despite normalising concentrations of IGF-1, individualised regimens of GH replacement do not reduce concentrations of myostatin in blood or skeletal muscle. Ongoing hypersecretion of myostatin may explain why individually titrated GH replacement regimens are less effective than higher weight-based regimens in increasing skeletal muscle mass.

中文翻译：

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用血清IGF-1滴定的GH替代品不会降低血液或骨骼肌中肌生长抑制素的浓度。

目的

传统的基于体重的GH替代方案比目前推荐的方案更有效地逆转GH缺乏的成年人的骨骼肌丢失，后者需要增加GH的剂量以恢复血清IGF-1的浓度。虽然基于体重的治疗方案会增加IGF-1的浓度并降低肌生成抑制素的浓度，但不知道单独滴定的GH方案有效性降低是否是由于肌生长抑制素的持续过度分泌所致。因此，本研究的目的是确定在缺乏GH的成年人中血液和骨骼肌中肌生长抑制素的浓度是否增加，以及通过滴定GH替代疗法以恢复血清IGF-1而降低这些浓度。

设计

对26名GH缺乏的成年人（18名男性和8名女性）进行了个性化的重组人GH治疗，目的是使IGF-1的血清浓度达到年龄和性别校正平均值的一个标准差之内。在基线时测量了肌生长抑制素的血浆浓度，并在治疗6个月后与15名健康对照（9名男性和6名女性）进行了比较。在这些GH缺乏的成年人中有19位（15名男性和4名女性）和10名健康对照组（6名男性和4名女性）进行了骨骼肌活检。通过qPCR确定IGF-1和肌生长抑制素mRNA的表达。

结果

在基线时，GH缺乏的成年人血清中IGF-1和骨骼肌mRNA的浓度降低，血浆中肌生长抑制素的浓度和骨骼肌mRNA的浓度升高（ 与健康对照组相比，P <.05）。尽管恢复了IGF-1的浓度，但GH替代并未降低血液或骨骼肌中肌生长抑制素的浓度。基线时GH缺乏的成年人中血液和骨骼肌中IGF-1和肌生长抑制素的浓度呈正相关（P  <.05），而GH缺乏的成年人则没有。

结论

缺乏GH的成年人血液和骨骼肌中肌生长抑制素的浓度增加。尽管IGF-1浓度正常化，但是GH替代疗法的个体化治疗并不能降低血液或骨骼肌中肌生长抑制素的浓度。持续的肌生长抑制素分泌过多可能可以解释为什么单独滴定的GH替代治疗方案在增加骨骼肌质量方面不如基于体重的较高治疗方案有效。