Sex- and stress-steroids interactions and the immune system: evidence for a neuroendocrine-immunological sexual dimorphism.
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.
Gaillard
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RC
Division of Endocrinology, Diabetology and Metabolism, University Hospital (CHUV), Lausanne, Switzerland.
Spinedi
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E
D000818:Animals; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000276:immunology / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D015213:Neuroimmunomodulation / Q000276:immunology* / Q000502:physiology; D009490:Neurosecretory Systems / Q000276:immunology* / Q000502:physiology; D009919:Orchiectomy; D010052:Ovariectomy; D010913:Pituitary-Adrenal System / Q000276:immunology / Q000502:physiology; D012727:Sex Characteristics; D013312:Stress, Physiological / Q000276:immunology*; D013739:Testosterone / Q000494:pharmacology / Q000627:therapeutic use
D004731:Endotoxins; D012739:Gonadal Steroid Hormones; D008070:Lipopolysaccharides; D013739:Testosterone; D003345:Corticosterone