Regulation of juvenile hormone titers in mosquitoes

描述(申请人提供)：蚊子传播的寄生虫病是世界上死亡和发病的主要原因之一。最近疟疾和登革热等蚊媒疾病发病率的急剧上升，以及蚊子对杀虫剂的广泛抗药性，突显了以蚊子专属制剂为基础的昆虫控制新方法的必要性。这种针对蚊子的控制剂的发现有赖于对蚊子生物学的基础研究。保幼激素(JH)是昆虫体内一种主要的激素调节物质。在雌性蚊子中，JH发出完成蜕皮到成虫阶段的信号，并启动生殖过程。JH滴度基本上由舌体(CA)合成JH的速率决定。CA活性的速率反过来又受起抑制或促进作用的丙二醛调节多肽的调节。在这个项目的前三年中，我们描述了促生长激素(AT)刺激和抑制素-C(AS-C)抑制JH的合成，幼虫阶段积累的营养物质调节CA活性，并首次对昆虫内分泌腺进行了基因组分析。在此基础上，我们提出脑释放的AT和AS对成年雌蚊JH合成的激活和调控是必不可少的。这些多肽的合成和释放与营养信号有关。因此，JH是将营养状态的变化与生殖期间特定生理事件的激活联系起来的转导机制的重要组成部分。这个项目的目标是了解多肽如何调节蚊子体内JH的合成。这个项目的最终目的是揭示蚊子营养状态的变化是如何被评估的，以及这些信息是如何被传递给CA的。为了验证这一模型，在本应用中，我们建议：1.研究AT和AS-C对JH合成的调控机制。2.研究脑内AT、AS-C合成和释放的营养调控。了解神经肽生理作用的分子基础将指导我们设计新的和负担得起的媒介控制试剂。

DESCRIPTION (provided by applicant): Mosquito-transmitted parasitic diseases are among the major causes of mortality and morbidity in the world. Recent dramatic increases in the incidence of mosquito-borne diseases, like malaria and dengue fever, and the wide-spread resistance of mosquitoes to insecticides underscores the need for new approaches to insect control based on mosquito- specific agents. The discovery of such mosquito-specific control agents depends on basic research on the biology of mosquitoes. Juvenile hormone (JH) is a major hormonal regulator in insects. In the female mosquito, JH signals the completion of the ecdysis to the adult stage, and initiates reproductive processes. JH titer is essentially determined by the rate at which the corpora allata (CA) synthesizes JH. The rate of CA activity is, in turn, regulated by allato-regulatory peptides that exert either allatostatic (inhibitory) or allatotropic (stimulatory) activities. During the first three years of this project we have described that allatotropin (AT) stimulates and allatostatin-C (AS-C) inhibits JH synthesis, that nutrients accumulated during the larval stages regulate CA activity, and also performed the first genomic analysis of an insect endocrine gland. Based on this work we propose that AT and AS released by the brain are essential for the activation and modulation of JH synthesis in adult female mosquitoes. The synthesis and release of these peptides is connected to nutritional signals. JH is therefore an important part of a transduction mechanism that connects changes in the nutritional status with activation of specific physiological events during reproduction. The goal of this project is to understand how peptides regulate the synthesis of JH in mosquitoes. The ultimate aim of this project is to reveal how changes in the mosquito's nutritional status are assessed and how this information is transduced to the CA. In order to test this model, in this application we propose to: 1. Investigate the mechanisms of control of JH synthesis by AT and AS-C. 2. Study the nutritional regulation of synthesis and release of AT and AS-C in the brain. Understanding the molecular basis of the physiological action of neuro-peptides will guide us in designing new and affordable agents for vector control.