Forkhead transcription factor FOXO1 is involved in hypoxia/reoxygenation-induced gonadotropin-releasing hormone decline. Issue 18 (16th December 2020)

• Record Type: Journal Article
• Authors: Shi, Chun; Li, Guihua; Guo, Han; Liu, Xintong
• Is Part Of: NeuroReport. Volume 31:Issue 18(2020)
• Publication Date: 2020-12-16
• Subjects: forkhead box protein O1 -- gonadotropin-releasing hormone -- hypoxia/reoxygenation -- nuclear factor-κB; Neurosciences -- Periodicals; Nervous system -- Periodicals; Neurophysiology -- Periodicals; Nervous System Diseases -- Periodicals; Nervous System Physiological Phenomena -- Periodicals; Neurosciences -- Periodicals; 616.805
• DOI: 10.1097/WNR.0000000000001548
• Languages: English
• ISSNs: 0959-4965

Abstract

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.