Previously, it has been demonstrated that aging is associated with nuclear factor-κB (NF-κB)-mediated hypothalamic gonadotropin-releasing hormone (GnRH) decrease. The hypothalamus is one of the brain regions that are vulnerable to… Click to show full abstract
Previously, it has been demonstrated that aging is associated with nuclear factor-κB (NF-κB)-mediated hypothalamic gonadotropin-releasing hormone (GnRH) decrease. The hypothalamus is one of the brain regions that are vulnerable to ischemia-reperfusion injury. However, it is unclear whether ischemia-reperfusion has an influence on the hypothalamic GnRH release. In the current study, GT1-7 cells, which are a cell line of hypothalamic GnRH neurons, were subjected to hypoxia-reoxygenation to mimic ischemia-reperfusion. The effect of hypoxia-reoxygenation on the hypothalamic GnRH release was investigated. It was found that GnRH secretion from GT1-7 cells was decreased under the hypoxia-reoxygenation condition. Mechanistic studies revealed that hypoxia-reoxygenation activated nuclear factor-κB (NF-κB) via the protein kinase B (Akt)/forkhead box protein O1 (FOXO1) pathway, thereby inhibiting gnrh1 gene. The results of the current study suggested that hypoxia-reoxygenation injury may facilitate the hypothalamic programming of system aging through impairment of hypothalamic GnRH release.
               
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