Department of Anatomy, Dali University, Dali, Yunnan, China.
Physiol Res. 2022 Aug 31;71(4):509-516. doi: 10.33549/physiolres.934861. Epub 2022 Jun 30.
Recent studies have suggested that the hypothalamus has an important role in aging by regulating nuclear factor-?B (NF-?B)-directed gonadotropin-releasing hormone (GnRH) decline. Moreover, our previous study has shown that ischemia-reperfusion (IR) injury activates NF-?B to reduce hypothalamic GnRH release, thus suggesting that IR injury may facilitate hypothalamic programming of system aging. In this study, we further examined the role of phosphoinositide 3-kinase (PI3K)/Protein kinase B (Akt) pathway, a critical intracellular signal pathway involved in the repair process after IR, in hypoxia-reoxygenation (HR)-associated GnRH decline in vitro. We used GT1-7 cells and primarily-cultured mouse GnRH neurons as cell models for investigation. Our data revealed that the activation of the PI3K/Akt/Forkhead box protein O3a (FOXO3a) pathway protects GnRH neurons from HR-induced GnRH decline by preventing HR-induced gnrh1 gene inhibition and NF-?B activation. Our results further the understanding of the regulatory mechanisms of HR-associated hypothalamic GnRH decline.
最近的研究表明，下丘脑通过调节核因子-?B（NF-?B）指导的促性腺激素释放激素（GnRH）下降在衰老中起重要作用。此外，我们之前的研究表明，缺血再灌注（IR）损伤会激活 NF-?B 以减少下丘脑 GnRH 的释放，这表明 IR 损伤可能促进下丘脑对系统衰老的编程。在这项研究中，我们进一步研究了磷酸肌醇 3-激酶（PI3K）/蛋白激酶 B（Akt）通路的作用，该通路是 IR 后修复过程中涉及的关键细胞内信号通路，在体外缺氧再复氧（HR）相关 GnRH 下降中发挥作用。我们使用 GT1-7 细胞和原代培养的小鼠 GnRH 神经元作为细胞模型进行研究。我们的数据表明，PI3K/Akt/叉头框蛋白 O3a（FOXO3a）通路的激活通过阻止 HR 诱导的 gnrh1 基因抑制和 NF-?B 激活来保护 GnRH 神经元免受 HR 诱导的 GnRH 下降。我们的结果进一步了解了 HR 相关下丘脑 GnRH 下降的调节机制。
