Shi Chun, Shi Rongjie, Guo Han
Department of Neurology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong.
Department of Anatomy, Dali University, Dali, Yunan.
Neuroreport. 2020 Apr 8;31(6):473-477. doi: 10.1097/WNR.0000000000001424.
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.
研究发现，下丘脑有助于控制衰老，而下丘脑驱动的程序性衰老与核因子κB（NF-κB）介导的促性腺激素释放激素（GnRH）减少有关。然而，衰老相关的下丘脑GnRH下降的分子机制在很大程度上尚不清楚。叉头框O（FOXO）是一类转录因子，已被证明与衰老有关。本研究使用GnRH神经元细胞系GT1-7来确定FOXO1是否参与肿瘤坏死因子α（TNF-α）诱导的GnRH减少。我们的数据表明，TNF-α通过抑制FOXO1的磷酸化来增加其活性。FOXO1活性增加抑制gnrh1基因并激活NF-κB，从而损害GT1-7细胞中GnRH的分泌。FOXO1活性的增加导致TNF-α诱导的GnRH释放减少，这可能突出了这一事件对衰老发展和针对年龄依赖性病理的治疗干预的重要性。
