Regulation of murine skeletal muscle growth by STAT5B is age- and sex-specific
Regulation of murine skeletal muscle growth by STAT5B is age- and sex-specific
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DOI：
10.1186/s13395-019-0204-3
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发表时间：
2019-06-24
期刊：
影响因子：
4.9
通讯作者：
McMahon, Chris D.
中科院分区：
文献类型：
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作者：
Paul, Ryan G.;Hennebry, Alex S.;McMahon, Chris D.
性二态生长与生长激素(GH)/胰岛素样生长因子1(IGF1)轴有关，尤其是GH诱导的细胞内信号转导和转录激活子5B(STAT5B)的激活，因为STAT5B的缺失使雄性小鼠的体重和骨骼肌质量减少到雌性小鼠的水平。然而，目前还不清楚为什么这些影响是性别和物种特有的，因为STAT5B的缺失会阻碍女孩的生长，但不会阻碍雄性小鼠的生长。我们的目的是确定STAT5B(-/-)小鼠骨骼肌性二态生长是否持续，并探讨STAT5B(-/-)调节性二态生长的机制。方法采集STAT5B(-/-)雄性和雌性STAT5B(-/-)小鼠及其野生型小鼠从青春期到成年期的血液和骨骼肌生长。结果STAT5B(-/-)小鼠的骨骼和骨骼肌生长都受到阻碍，但雄性更明显。尽管减少了，但在STAT5B(-/-)小鼠中，骨骼肌的性别二态生长持续存在，两性肌纤维的组成发生了氧化转变。在所有年龄段的雄性STAT5B(-/-)小鼠的血液和骨骼肌中IGF1的浓度都降低了，但只有雌性STAT5B(-/-)小鼠在青春期开始时才降低。雄性和雌性STAT5B(-/-)小鼠骨骼肌中雄激素受体(AR)和雌激素受体α(ER)的mRNA和蛋白表达分别降低。STAT5B基因缺失后，骨骼肌中肌生长抑素蛋白、细胞因子信号转导抑制因子2(SOCS2)的抑制子Ar、Er和细胞因子诱导的SH2蛋白(Cis)基因的性别二型性表达消失。结论STAT5B在各个年龄段的雄性小鼠骨骼肌中均参与GH信号的传递，但在雌性小鼠中仅在青春期前起作用。在雄性和雌性小鼠中，STAT5B似乎都在调节雄激素和雌激素的作用，但在STAT5B(-/-)小鼠中，性二态生长持续存在。
BackgroundSexually 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.MethodsBlood and skeletal muscle were harvested from male and female STAT5B(-/-) mice and their wild-type littermates from the onset of puberty to adulthood.ResultsGrowth 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 (ER) 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, Er, suppressor of cytokine signalling 2 (Socs2), and cytokine-inducible SH2-containing protein (Cis) mRNA in skeletal muscle.ConclusionsSTAT5B 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.