Department for Neurobiology, Institute for Biological Research "Sinisa Stankovic", National Institute of Republic of Serbia, University of Belgrade, 11060 Belgrade, Serbia.
Biomolecules. 2024 Aug 17;14(8):1020. doi: 10.3390/biom14081020.
Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system, usually diagnosed during the reproductive period. Both MS and its commonly used animal model, experimental autoimmune encephalomyelitis (EAE), exhibit sex-specific features regarding disease progression and disturbances in the neuroendocrine and endocrine systems. This study investigates the hypothalamic-pituitary-adrenal (HPA) axis response of male and female rats during EAE. At the onset of EAE, expression in the hypothalamus of both sexes is decreased, while males show reduced plasma adrenocorticotropic hormone levels. Adrenal gland activity is increased during EAE in both males and females, as evidenced by enlarged adrenal glands and increased StAR gene and protein expression. However, only male rats show increased serum and adrenal corticosterone levels, and an increased volume of the adrenal cortex. Adrenal 3β-HSD protein and progesterone levels are elevated in males only. Serum progesterone levels of male rats are also increased, although testicular progesterone levels are decreased during the disease, implying that the adrenal gland is the source of elevated serum progesterone levels in males. Our results demonstrate a sex difference in the response of the HPA axis at the adrenal level, with male rats showing a more pronounced induction during EAE.
多发性硬化症（MS）是一种影响中枢神经系统的慢性炎症性疾病，通常在生育期内诊断出来。MS 及其常用的动物模型实验性自身免疫性脑脊髓炎（EAE）在疾病进展和神经内分泌及内分泌系统紊乱方面都表现出性别特异性特征。本研究探讨了 EAE 期间雄性和雌性大鼠下丘脑-垂体-肾上腺（HPA）轴的反应。在 EAE 发病时，两性的下丘脑表达均降低，而雄性的血浆促肾上腺皮质激素水平降低。EAE 期间，男女两性的肾上腺活动均增加，表现为肾上腺增大，StAR 基因和蛋白表达增加。然而，只有雄性大鼠表现出血清和肾上腺皮质酮水平升高，以及肾上腺皮质体积增加。只有雄性大鼠的肾上腺 3β-HSD 蛋白和孕酮水平升高。雄性大鼠的血清孕酮水平也升高，尽管睾丸孕酮水平在疾病期间下降，这意味着在雄性中，升高的血清孕酮水平的来源是肾上腺。我们的研究结果表明，HPA 轴在肾上腺水平上的反应存在性别差异，雄性大鼠在 EAE 期间表现出更明显的诱导。
