Sexual dimorphism in the pituitary-adrenal response to tumor necrosis factor-alpha, but not to interleukin-6, in the rat.

It is known that the pituitary-adrenal responses to lipopolysaccharide and interleukin (IL)-1 are sexually dimorphic in rodents, with females having an enhanced secretion of adrenocorticotropin (ACTH) and corticosterone. This study investigated whether the ACTH and corticosterone responses to tumor necrosis factor (TNF)-alpha and IL-6, two principal proinflammatory cytokines, are also modulated by the sex steroid milieu in the rat. Mature male and female rats received an intravenous administration of TNF-alpha(10 microg/kg) and IL-6 (10 microg/kg), and changes in plasma ACTH and corticosterone levels were determined over time. The effect of gonadectomy on the hormonal responses was also examined in both sexes. TNF-alpha induced significantly higher responses of ACTH and corticosterone in females than in males, and this sexual difference was abolished by gonadectomy in both sexes. By contrast, the hormonal responses to IL-6 were not significantly affected by either gender or gonadectomy. These results suggest a sex steroid-dependent modulation of the TNF-alpha-induced, but not the IL-6-induced, ACTH and corticosterone secretion in the rat. Further evidence for the sexually dimorphic neuroimmunoendocrine activity is reported herein.