AMPK对黄体脂滴代谢与类固醇激素产生的调节作用

Regulatory effects of AMPK signaling on the metabolism of lipid droplets and the production of steroid hormones in the corpus luteum

黄体是卵巢重要的内分泌组织,含有丰富的脂滴,储存大量的胆固醇酯与甘油三酯,并参与卵巢功能调节。细胞质中的脂滴可作为细胞信号平台,与其他细胞器发生互作,同时参与控制细胞新陈代谢。促黄体素LH可以通过激活cAMP和PKA信号通路促进脂滴中水解胆固醇酯的激素敏感性脂肪酶(HSL)的磷酸化与激活,为类固醇激素生成提供胆固醇,为线粒体产生能量提供脂肪酸。能量传感器AMPK可以通过破坏代谢途径来抑制类固醇激素生成,如线粒体需要的胆固醇或类固醇激素生成所需的基因表达。另外,自噬也通过清除受损细胞器以及在饥饿时为细胞提供必需营养的方式参与调节细胞的代谢平衡,而影响AMPK活性与脂滴平衡的信号通路可以调控黄体细胞的自噬。由此可见,多个信号通路集中于黄体脂滴,参与调节类固醇激素生成和脂滴代谢。因此,进一步了解黄体细胞代谢通路是深入理解黄体功能与寿命调控机制的基础。

The corpus luteum is an important endocrine tissue in the ovary,which has abundant lipid droplets with cholesteryl esters and triglycerides and participates in the regulation of ovarian functions.The cytoplasmic lipid droplets can serve as a cell signaling platform for interactions with other organelles,and also regulate the cellular metabolism.LH can stimulate the phosphorylation and activation of hormone-sensitive lipase(HSL),an enzyme that hydrolyzes cholesteryl esters stored in lipid droplets through the activation of the cAMP and the protein kinase A(PKA)signaling pathway to provide cholesterol for steroidogenesis and fatty acids for utilization by mitochondria for energy production.The energy sensor AMP-activated protein kinase(AMPK)can inhibit steroidogenesis by interrupting metabolic pathways,such as the cholesterol supply for mitochondria and the gene expression for steroidogenesis.In additionally,the autophagy in luteal cells also regulates the metabolic balance of the cell by eliminating damaged organelles and providing cells with essential nutrients during starvation,which is regulated by signaling pathways that impact AMPK activity and lipid droplet homeostasis.Together,a number of signaling pathways converge on luteal lipid droplets to regulate steroidogenesis and metabolism.Therefore,research on metabolic pathways in luteal cells is fundamental to further understanding the mechanism that controls the function and lifespan of the corpus luteum.