Tumor necrosis factor α reduces gonadotropin-releasing hormone release through increase of forkhead box protein O1 activity. Issue 6 (8th April 2020)

• Record Type: Journal Article
• Authors: Shi, Chun; SHI, Rongjie; Guo, Han
• Is Part Of: NeuroReport. Volume 31:Issue 6(2020)
• Publication Date: 2020-04-08
• Subjects: aging -- forkhead box O -- gonadotropin-releasing hormone -- 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.0000000000001424
• Languages: English
• ISSNs: 0959-4965

Abstract

Abstract : It has been found that hypothalamus helps to control aging, and hypothalamus-driven programmatic aging is associated with nuclear factor-κB (NF-κB)-mediated decrease of gonadotropin-releasing hormone (GnRH). However, the molecular mechanism(s) underlying aging-associated hypothalamic GnRH decline are largely unknown. Forkhead box O (FOXO), a family of transcription factors, has been demonstrated to be associated with aging. GnRH neuronal cell line GT1-7 was used in this study to determine whether FOXO1 was involved in tumor necrosis factor α (TNF-α)-induced decrease of GnRH. Our data showed that FOXO1 activity was increased by TNF-α through inhibition of its phosphorylation. Increased FOXO1 activity inhibited gnrh1 gene and activated NF-κB, thereby impairing the secretion of GnRH from GT1-7 cells. The increase of FOXO1 activity contributes to TNF-α-induced decrease of GnRH release, which may underscore the significance of this event to the development of aging and therapeutic interventions against age-dependent pathologies.