PDF(Pubmed)
Abstract：
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 Ghrh and Sst in the hypothalamus does not change, except for Npy and Agrp, while at the pituitary level the Gh, Ghrhr and Ghr 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 Ghr and Igf1r 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.
摘要：
炎症，脱髓鞘,和中枢神经系统（CNS）的轴索损伤是多发性硬化症（MS）及其代表性动物模型的标志，实验性自身免疫性脑脊髓炎（EAE）。有科学证据表明生长激素（GH）参与自身免疫调节。关于GH/胰岛素样生长因子-1（IGF-1）轴与MS/EAE之间关系的先前数据尚无定论；因此，本研究的目的是研究急性单相EAE时GH轴的变化.结果表明，Ghrh和Sst基因在下丘脑中的表达没有改变，除了Npy和Agrp,而在垂体水平的Gh，Ghrhr和Ghr基因上调。有趣的是,在疾病的高峰期，垂体中的促生长素细胞的细胞体积保持不变。我们发现升高的血清GH水平与低IGF-1浓度和下调Ghr和Igf1r在肝脏中的表达有关。表明类似GH抵抗的情况。这可能是由于当CNS中的炎症最大时在疾病的高峰期营养摄入不足。考虑到GH分泌受到众多中枢和外周信号的精细调节，应彻底研究MS/EAE中GH/IGF-1轴的参与，以寻找未来可能的治疗策略，特别是为了改善EAE疾病。
