University of Auckland Waikato Clinical School, Hamilton, New Zealand.
ManukaMed LP, Hamilton, New Zealand.
J Endocrinol. 2021 Feb;248(2):207-220. doi: 10.1530/JOE-20-0485.
Insulin-like growth factor-1 (IGF1) is crucial for regulating post-natal growth and, along with myostatin (MSTN), regulates muscle size. Here, we sought to clarify the roles of these two genes in regulating sexually dimorphic growth of body and muscle mass. In the first study, we established that Igf1 mRNA was increased to a greater extent and Igf1 receptor mRNA increased earlier in male, than in female, gastrocnemius muscles during the rapid phase of growth (from 2 to 6 weeks) were unchanged, thereafter, to 32 weeks of age in WT mice (P < 0.001). In the second study, we sought to determine if supplemental IGF1 could overcome the sexual dimorphism of muscle and body mass, when myostatin is absent. We crossed myostatin null (Mstn-/-) mice with mice over-expressing Igf1 in skeletal muscle (Igf1+) to generate six genotypes; control (Mstn+/+), Mstn+/-, Mstn-/-, Mstn+/+:Igf1+, Mstn+/-:Igf1+ and Mstn-/-:Igf1+ (n = 8 per genotype and sex). In both sexes, body mass at 12 weeks was increased by at least 1.6-fold and muscle mass by at least 3-fold in Mstn-/-:Igf1+ compared with Mstn+/+ mice (P < 0.001). The abundance of AKT was increased in muscles of mice transgenic for Mstn, while phosphorylation of AKTS473 was increased in both male and female mice transgenic for Igf1+. The ratio of phosphorylated to total AKT was 1.9-fold greater in male mice (P < 0.001). Thus, despite increased growth of skeletal muscle and body size when myostatin was absent and IGF1 was in excess, sexual dimorphism persisted, an effect consistent with greater IGF1-induced activation of AKT in skeletal muscles of males.
胰岛素样生长因子 1（IGF1）对于调节出生后的生长至关重要，它与肌肉生长抑制素（MSTN）一起调节肌肉大小。在这里，我们试图阐明这两个基因在调节身体和肌肉质量的性别二态性生长中的作用。在第一项研究中，我们发现 IGF1mRNA 在雄性比在雌性的腓肠肌中增加的幅度更大，并且 IGF1 受体 mRNA 在快速生长期（从 2 到 6 周）增加得更早，此后，在 WT 小鼠中，到 32 周龄时不变（P<0.001）。在第二项研究中，我们试图确定在缺乏肌肉生长抑制素的情况下，补充 IGF1 是否可以克服肌肉和体重的性别二态性。我们将肌肉生长抑制素缺失（Mstn-/-）的小鼠与肌肉中过表达 IGF1 的小鼠（Igf1+）杂交，生成六种基因型；对照（Mstn+/+）、Mstn+/-、Mstn-/-、Mstn+/+:Igf1+、Mstn+/-:Igf1+和 Mstn-/-:Igf1+（每种基因型和性别各 8 只）。在两种性别中，Mstn-/-:Igf1+的体重在 12 周时增加了至少 1.6 倍，肌肉量增加了至少 3 倍，与 Mstn+/+的小鼠相比（P<0.001）。在肌肉生长抑制素转基因小鼠中，AKT 的丰度增加，而在 IGF1 转基因雄性和雌性小鼠中，AKTS473 的磷酸化增加。在雄性小鼠中，磷酸化的 AKT 与总 AKT 的比值增加了 1.9 倍（P<0.001）。因此，尽管当肌肉生长抑制素缺失和 IGF1 过剩时，骨骼肌和身体大小的生长增加，但性别二态性仍然存在，这一效应与 IGF1 诱导的 AKT 在雄性骨骼肌中的激活增加一致。
