Repeated endotoxin treatment decreases immune and hypothalamo-pituitary-adrenal axis responses: effects of orchidectomy and testosterone therapy

It is known that in vivo administration of bacterial endotoxin activates immune cells to release cytokines, these substances in turn enhancing hypothalamo-pituitary-adrenal (HPA) axis function; additional evidence supports the existence of an immune-neuroendocrine sexual dimorphism. In the present study, we investigated: (1) the in vivo response of both the HPA and the immune systems to single and repeated endotoxin administrations in mice, and (2) whether testosterone possesses a modulatory effect on neuroendocrine-immune function under endotoxemia. For these purposes, adult male BALB/c mice were orchidectomized (Odx) or sham-operated and injected s.c., on alternate days, with either corn oil alone (Odx and Sham) or containing 20 micrograms of testosterone (Odx+T) until animals were killed. One week after surgery, different groups of mice were treated i.p. with bacterial lipopolysaccharide (LPS; 25 micrograms per mouse) in a single (day 1, D1) or repeated (at 24-hour intervals for 5 consecutive days) form. Animals were decapitated (on D1, D3 and D5 of the treatment) 2 h after the last injection of either vehicle alone or containing LPS (the two groups were run in parellel). Trunk blood was collected and the whole medial basal hypothalamus (wMBH), the anterior pituitary (AP) and adrenal glands were dissected. Plasma tumor necrosis factor-alpha (TNF alpha), ACTH and corticosterone (B) concentrations as well as wMBH CRH, AP ACTH and adrenal B contents were determined by specific assays.(ABSTRACT TRUNCATED AT 250 WORDS