Forkhead transcription factor FOXO1 is involved in hypoxia/reoxygenation-induced gonadotropin-releasing hormone decline.

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.

• Authors: Chun Shi, Guihua Li, Han Guo, Xintong Liu
• Journal: Neuroreport (Neuroreport) Vol. 31 Issue 18 Pg. 1296-1301 (12 16 2020) ISSN: 1473-558X [Electronic] England
• PMID: 33165202 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Forkhead Box Protein O1
• Foxo1 protein, mouse
• NF-kappa B
• Protein Precursors
• progonadoliberin I
• Gonadotropin-Releasing Hormone
• Proto-Oncogene Proteins c-akt

Topics

• Aging (genetics, metabolism)
• Animals
• Cell Line
• Forkhead Box Protein O1 (metabolism)
• Gene Knockdown Techniques
• Gonadotropin-Releasing Hormone (genetics, metabolism)
• Hypothalamus (cytology, metabolism)
• Hypoxia (metabolism)
• Mice
• NF-kappa B (metabolism)
• Promoter Regions, Genetic
• Protein Precursors (genetics)
• Proto-Oncogene Proteins c-akt (metabolism)
• Reperfusion Injury (genetics, metabolism)
• Transcription, Genetic