Department of Neurobiology, Institute for Biological Research "Sinisa Stankovic"-National Institute of Republic of Serbia, University of Belgrade, 11108 Belgrade, Serbia.
Department of Cytology, Institute for Biological Research "Sinisa Stankovic"-National Institute of Republic of Serbia, University of Belgrade, 11108 Belgrade, Serbia.
Int J Mol Sci. 2024 May 27;25(11):5837. doi: 10.3390/ijms25115837.
Inflammation, demyelination, and axonal damage to the central nervous system (CNS) are the hallmarks of multiple sclerosis (MS) and its representative animal model, experimental autoimmune encephalomyelitis (EAE). There is scientific evidence for the involvement of growth hormone (GH) in autoimmune regulation. Previous data on the relationship between the GH/insulin like growth factor-1 (IGF-1) axis and MS/EAE are inconclusive; therefore, the aim of our study was to investigate the changes in the GH axis during acute monophasic EAE. The results show that the gene expression of and in the hypothalamus does not change, except for and , while at the pituitary level the , and genes are upregulated. Interestingly, the cell volume of somatotropic cells in the pituitary gland remains unchanged at the peak of the disease. We found elevated serum GH levels in association with low IGF-1 concentration and downregulated and expression in the liver, indicating a condition resembling GH resistance. This is likely due to inadequate nutrient intake at the peak of the disease when inflammation in the CNS is greatest. Considering that GH secretion is finely regulated by numerous central and peripheral signals, the involvement of the GH/IGF-1 axis in MS/EAE should be thoroughly investigated for possible future therapeutic strategies, especially with a view to improving EAE disease.
中枢神经系统(CNS)的炎症、脱髓鞘和轴突损伤是多发性硬化症(MS)及其代表性动物模型实验性自身免疫性脑脊髓炎(EAE)的特征。有科学证据表明生长激素(GH)参与自身免疫调节。先前关于 GH/胰岛素样生长因子-1(IGF-1)轴与 MS/EAE 之间关系的数据尚无定论;因此,我们的研究目的是调查急性单相 EAE 期间 GH 轴的变化。结果表明,除了 和 外,下丘脑的 和 基因表达没有改变,而在垂体水平, 、 和 基因上调。有趣的是,在疾病高峰期,垂体中生长激素细胞的细胞体积保持不变。我们发现血清 GH 水平升高与 IGF-1 浓度降低以及肝脏中 和 表达下调有关,表明存在类似于 GH 抵抗的情况。这可能是由于在中枢神经系统炎症最严重时疾病高峰期的营养摄入不足所致。考虑到 GH 的分泌受到许多中枢和外周信号的精细调节,GH/IGF-1 轴在 MS/EAE 中的参与应该得到彻底研究,以寻找可能的未来治疗策略,特别是为了改善 EAE 疾病。