Gaillard R C, Spinedi E
Division of Endocrinology, Diabetology and Metabolism, University Hospital (CHUV), Lausanne, Switzerland.
Domest Anim Endocrinol. 1998 Sep;15(5):345-52. doi: 10.1016/s0739-7240(98)00028-9.
It is well established that sexual dimorphism exits within the immune system. Females have higher levels of immunoglobulins, greater antibody response to antigens, and higher incidence of autoimmune diseases, such as systemic lupus erythematosus, Grave's disease, and Hashimoto thyroiditis than males. Spontaneous autoimmune syndromes in mice are more prevalent and of greater severity in females compared with males, and the course of the disease can be modulated by changes in levels of gonadal steroids. A sexual dimorphism is also present in the pituitary-adrenal function: females have higher corticosterone levels and higher corticosteroidogenesis. In the context of the immune-neuroendocrine interactions, we investigated the effects of gonadectomy and sex hormone therapy on endotoxin-stimulated hypothalamo-pituitary-adrenal axis. Whereas endotoxin-induced corticosterone release is invariable throughout the different stages of the oestrus cycle, gonadectomy in both male and female mice leads to enhanced adrenal and immune responses to endotoxin. Interestingly, these enhanced adrenal and immune responses can be completely reversed by testosterone treatment regardless of the sex of the mice. Studies performed over development confirm the role of endogenous testosterone in modulating the endotoxin-induced corticosterone secretion. Indeed, corticosterone response to endotoxin is maximal before puberty when endogenous testosterone levels are low and declines in postpubertal and adult mice. In conclusion, all these data support a sex steroid hormone basis for a neuroendocrine-immunologic sexual dimorphism.
免疫系统中存在性二态性，这一点已得到充分证实。女性的免疫球蛋白水平更高，对抗原的抗体反应更强，自身免疫性疾病的发病率也更高，如系统性红斑狼疮、格雷夫斯病和桥本甲状腺炎等，均高于男性。与雄性小鼠相比，雌性小鼠的自发性自身免疫综合征更为普遍且病情更严重，疾病进程可通过性腺类固醇水平的变化进行调节。垂体 - 肾上腺功能也存在性二态性：女性的皮质酮水平更高，皮质类固醇生成能力更强。在免疫 - 神经内分泌相互作用的背景下，我们研究了去势和性激素治疗对内毒素刺激的下丘脑 - 垂体 - 肾上腺轴的影响。内毒素诱导的皮质酮释放在发情周期的不同阶段是恒定的，而雄性和雌性小鼠去势后都会导致肾上腺和免疫系统对内毒素的反应增强。有趣的是，无论小鼠性别如何，睾酮治疗都能完全逆转这些增强的肾上腺和免疫反应。在发育过程中进行的研究证实了内源性睾酮在调节内毒素诱导的皮质酮分泌中的作用。实际上，在内源性睾酮水平较低的青春期前，皮质酮对内毒素的反应最大，而在青春期后和成年小鼠中则下降。总之，所有这些数据支持了神经内分泌 - 免疫性二态性的性类固醇激素基础。
