The Aedes aegypti mosquito is the principal vector for many dangerous human viral diseases. Carbohydrate metabolism (CM) is essential for supplying the energy necessary for host seeking, blood digestion and rapid egg development of this vector insect. The steroid hormone 20-hydroxyecdysone (20E) and the ecdysone receptor (EcR) are important regulators of CM, coordinating it with female reproductive events. We report here that the NR4A nuclear receptor AHR38 plays a critical role in mediating these actions of 20E and EcR. AHR38 RNA interference (RNAi) depletion in female mosquitoes blocked the transcriptional activation of CM genes encoding phosphoglucomutase (PGM) and trehalose-6-phophate synthase (TPS); it caused an increase of glycogen accumulation and a decrease of the circulating sugar trehalose. This treatment also resulted in a dramatic reduction in fecundity. Considering that these phenotypes resulting from AHR38 RNAi depletion are similar to those of EcR RNAi, we investigated a possible connection between these transcription factors in CM regulation. EcR RNAi inhibits the AHR38 gene expression. Moreover, the 20E-induced EcR complex directly activates AHR38 by binding to the ecdysone response element (EcRE) in the upstream regulatory region of this gene. The present work has implicated AHR38 in the 20E-mediated control of CM and provided new insight into mechanisms of 20E regulation of metabolism during female mosquito reproduction.

在埃及伊蚊蚊子是许多危险的人类病毒性疾病的主要载体。碳水化合物代谢（CM）对于提供该媒介昆虫的宿主寻求，血液消化和快速卵子发育所必需的能量至关重要。类固醇激素20-羟基蜕皮激素（20E）和蜕皮激素受体（EcR）是CM的重要调节剂，可与女性生殖活动相协调。我们在这里报告说，NR4A核受体AHR38在介导20E和EcR的这些作用中起着关键作用。AHR38雌性蚊子中的RNA干扰（RNAi）耗竭阻止了编码磷酸葡萄糖突变酶（PGM）和海藻糖6磷酸合酶（TPS）的CM基因的转录激活；它导致糖原积累的增加和循环糖海藻糖的减少。这种治疗还导致生育力显着降低。考虑到从产生这些表型AHR38的RNAi枯竭类似于那些EcR的RNA干扰，我们研究了CM调控这些转录因子之间可能的联系。的EcR的RNAi抑制AHR38基因表达。此外，20E诱导的EcR复合物直接激活AHR38通过与该基因上游调控区中的蜕皮激素响应元件（EcRE）结合。目前的工作牵连AHR38在20E介导的CM的控制，并提供了对女性蚊子繁殖过程中20E代谢调控机制的新见解。