AgResearch Ltd, Ruakura Research Centre, Private Bag 3123, Hamilton, New Zealand.
Faculty of Medical & Health Sciences, Waikato Clinical Campus, University of Auckland, Private Bag 3200, Hamilton, 3240, New Zealand.
Skelet Muscle. 2019 Jun 24;9(1):19. doi: 10.1186/s13395-019-0204-3.
Sexually dimorphic growth has been attributed to the growth hormone (GH)/insulin-like growth factor 1 (IGF1) axis, particularly GH-induced activation of the intracellular signal transducer and activator of transcription 5B (STAT5B), because deletion of STAT5B reduces body mass and the mass of skeletal muscles in male mice to that in female mice. However, it remains unclear why these effects are sex- and species-specific, because the loss of STAT5B retards growth in girls, but not in male mice. Our objectives were to determine whether sexually dimorphic growth of skeletal muscle persisted in STAT5B mice and investigate the mechanisms by which STAT5B regulates sexually dimorphic growth.
Blood and skeletal muscle were harvested from male and female STAT5B mice and their wild-type littermates from the onset of puberty to adulthood.
Growth of the skeleton and skeletal muscles was retarded in both sexes of STAT5B mice, but more so in males. Although reduced, sexually dimorphic growth of skeletal muscle persisted in STAT5B mice with an oxidative shift in the composition of myofibres in both sexes. Concentrations of IGF1 in blood and skeletal muscle were reduced in male STAT5B mice at all ages, but only in female STAT5B mice at the onset of puberty. Expression of androgen receptor (AR) and oestrogen receptor alpha (ERα) mRNA and protein was reduced in skeletal muscles of male and female STAT5B mice, respectively. Loss of STAT5B abolished the sexually dimorphic expression of myostatin protein and Igf1, Ar, Erα, suppressor of cytokine signalling 2 (Socs2), and cytokine-inducible SH2-containing protein (Cis) mRNA in skeletal muscle.
STAT5B appears to mediate GH signalling in skeletal muscles of male mice at all ages, but only until puberty in female mice. STAT5B also appears to mediate the actions of androgens and oestrogens in both male and female mice, but sexually dimorphic growth persists in STAT5B mice.
性别二态性生长归因于生长激素（GH）/胰岛素样生长因子 1（IGF1）轴，特别是 GH 诱导的细胞内信号转导子和转录激活子 5B（STAT5B）的激活，因为 STAT5B 的缺失会降低雄性小鼠的体重和骨骼肌质量，使其与雌性小鼠相当。然而，目前尚不清楚为什么这些影响具有性别和物种特异性，因为 STAT5B 的缺失会减缓女孩的生长，但不会减缓雄性小鼠的生长。我们的目的是确定 STAT5B 小鼠是否存在骨骼肌性别二态性生长，并研究 STAT5B 调节性别二态性生长的机制。
从青春期开始到成年期，从雄性和雌性 STAT5B 小鼠及其野生型同窝仔鼠中采集血液和骨骼肌。
STAT5B 小鼠的骨骼和骨骼肌生长均受到抑制，但雄性更为明显。尽管有所减少，但 STAT5B 小鼠的骨骼肌仍存在性别二态性生长，且两种性别中的肌纤维组成均发生氧化转变。雄性 STAT5B 小鼠在所有年龄段的血液和骨骼肌中的 IGF1 浓度均降低，但仅在青春期的雌性 STAT5B 小鼠中降低。雄性和雌性 STAT5B 小鼠的骨骼肌中雄激素受体（AR）和雌激素受体α（ERα）mRNA 和蛋白的表达均降低。STAT5B 的缺失消除了肌肉生长抑制素蛋白和 Igf1、Ar、Erα、细胞因子信号转导抑制因子 2（Socs2）和细胞因子诱导的 SH2 含有蛋白（Cis）mRNA 在骨骼肌中的性别二态性表达。
STAT5B 似乎在雄性小鼠的骨骼肌中介导 GH 信号转导，在所有年龄段均如此，但仅在雌性小鼠的青春期如此。STAT5B 似乎还介导雄激素和雌激素在雄性和雌性小鼠中的作用，但 STAT5B 小鼠中的性别二态性生长仍然存在。
