Sieber Matthew H, Spradling Allan C
Howard Hughes Medical Institute Research Laboratory, Department of Embryology, Carnegie Institution for Science, 3520 San Martin Drive, Baltimore, MD 21218, USA.
Howard Hughes Medical Institute Research Laboratory, Department of Embryology, Carnegie Institution for Science, 3520 San Martin Drive, Baltimore, MD 21218, USA.
Curr Biol. 2015 Apr 20;25(8):993-1004. doi: 10.1016/j.cub.2015.02.019. Epub 2015 Mar 19.
Disruptions in energy homeostasis severely affect reproduction in many organisms and are linked to several reproductive disorders in humans. As a result, understanding the mechanisms that control nutrient accumulation in the oocyte will provide valuable insights into the links between metabolic disease and reproductive dysfunction. We show that the steroid hormone ecdysone functions in Drosophila to control lipid metabolism and support oocyte production. First, local EcR-mediated signaling induces a stage-specific accumulation of lipids in stage-10 oocytes. EcR induces lipid accumulation by promoting the activation of the lipogenic transcription factor SREBP and by controlling the expression of the low-density lipoprotein (LDL) receptor homolog, LpR2. Second, global signaling via the ecdysone receptor, EcR, establishes a female metabolic state and promotes whole-body triglyceride and glycogen storage at high levels. EcR acts in the CNS to mediate these effects, in part by promoting higher levels of feeding in females. Thus, ecdysone functions at two levels to support reproduction: first by inducing lipid accumulation in the late stages of oocyte development and second by providing a signal that coordinates lipid metabolism in the germline with whole-animal lipid homeostasis. Ecdysone regulation allows females to assess the demands of oogenesis and alter their behavior and metabolic state to support the biosynthetic requirements of oocyte production.
能量稳态的破坏会严重影响许多生物体的繁殖，并与人类的几种生殖障碍有关。因此，了解控制卵母细胞中营养物质积累的机制将为深入了解代谢疾病与生殖功能障碍之间的联系提供有价值的见解。我们发现，类固醇激素蜕皮激素在果蝇中发挥作用，控制脂质代谢并支持卵母细胞的产生。首先，局部EcR介导的信号传导诱导10期卵母细胞中脂质的阶段特异性积累。EcR通过促进脂肪生成转录因子SREBP的激活以及控制低密度脂蛋白（LDL）受体同源物LpR2的表达来诱导脂质积累。其次，通过蜕皮激素受体EcR的全局信号传导建立雌性代谢状态，并促进全身甘油三酯和糖原的高水平储存。EcR在中枢神经系统中发挥作用以介导这些效应，部分是通过促进雌性更高水平的进食来实现的。因此，蜕皮激素在两个层面发挥作用以支持繁殖：首先是在卵母细胞发育后期诱导脂质积累，其次是提供一个信号，将生殖系中的脂质代谢与全动物脂质稳态协调起来。蜕皮激素调节使雌性能够评估卵子发生的需求，并改变其行为和代谢状态，以支持卵母细胞产生的生物合成需求。
