BACKGROUND:The hippocampus regulates the hypothalamic-pituitary-adrenal axis through negative feedback.The hypothalamic paraventricular nucleus receives neuronal input from the hippocampus via the fornix. OBJECTIVE:To explore whether the negative feedback effect of the hippocampus on the hypothalamic-pituitary-adrenal axis is contributed to the inhibitory effect of mineralocorticoid receptor (MR) and glucocorticoid receptor(GR) in the hippocampus on the paraventricular nucleus via the fornix. DESIGN,TIME AND SETTING:Randomized,controlled,animal experiment.The study was performed at the Department of Histology and Embryology,China Medical University between September 2006 and September 2008. MATERIALS:Rabbit anti-rat anti-MR and rabbit anti-rat anti-GR antibodies were purchased from Santa Cruz Biotechnology,USA.Rabbit anti-rat anti-corticotrophin releasing hormone(CRH) and rabbit anti-rat anti-arginine vasopressin antibodies were purchased from Wuhan Boster. METHODS:A total of 90 male,Wistar rats were randomly divided into model and sham-surgery groups(n=45).Fornix transection was performed in the model group,while the sham-surgery group underwent surgery,but no fornix transection. MAIN OUTCOME MEASURES:Immunohistochemistry was used to examine MR and GR expression in the hippocampus,as well as CRH and anti-arginine vasopressin in the paraventricular nucleus.Western blot was used to measure alterations in MR,GR,and CRH protein expression following fomix transection. RESULTS:Compared with the sham-surgery group,there were no obvious changes in MR and GR expression in the hippocampus,or CRH and anti-arginine vasopressin expression in the paraventricular nucleus within 4 days of fornix transection.However,after 7-10 days,significantly decreased MR and GR expression in the hippocampus,and increased CRH and anti-arginine vasopressin expression in the paraventricular nucleus were observed(P<0.05-0.01). CONCLUSION:Negative feedback from the hippocampus on the hypothalamic-pituitary-adrenal axis might be mediated through the fornix,and the corticosterone actions mediated by hippocampal corticosteroid receptors indirectly modulated the hypothalamic-pituitary-adrenal axis. BACKGROUND: The hippocampus regulates the hypothalamic-pituitary-adrenal axis through negative feedback. The hypothalamic paraventricular nucleus received neuronal input from the hippocampus via the fornix. OBJECTIVE: To explore whether the negative feedback effect of the hippocampus on the hypothalami-pituitary-adrenal axis is contributed to the inhibitory effect of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the hippocampus on the paraventricular nucleus via the fornix. DESIGN, TIME AND SETTING: Randomized, controlled, animal experiment. The study was performed at the Department of Histology and Embryology, China Medical University between September 2006 and September 2008. MATERIALS: Rabbit anti-rat anti-MR and rabbit anti-rat anti-GR antibodies were purchased from Santa Cruz Biotechnology, USA. Rabbit anti-rat anti-corticotrophin releasing hormone (CRH) and rabbit anti-rat anti-arginine vasopressin antibodies were purchased from Wuhan Boster. METHODS: A total of 90 male, W istar rats were randomly divided into model and sham-surgery groups (n = 45). Fornix transection was performed in the model group, while the sham-surgery group underwent surgery, but no fornix transection. MAIN OUTCOME MEASURES: Immunohistochemistry was used to examine MR and GR expression in the hippocampus, as well as CRH and anti-arginine vasopressin in the paraventricular nucleus. Western blot was used to measure alterations in MR, GR, and CRH protein expression following fomix transection. RESULTS: Compared with the sham-surgery group, there were no obvious changes in MR and GR expression in the hippocampus, or CRH and anti-arginine vasopressin expression in the paraventricular nucleus within 4 days of fornix transection. Despite, after 7-10 days, and significantly reduced MR and GR expression in the hippocampus, and increased CRH and anti-arginine vasopressin expression in the paraventricular nucleus were observed (P <0.05-0.01). CONCLUSION: Negative feedback from the hippocampus on the hypothalamic-pituitary-adrenal axis might be mediated through the fornix, and the corticosterone actions mediated by hippocampal corticosteroid receptors alone modulated the hypothalamic-pituitary-adrenal axis.