Regulation of juvenile hormone titers in mosquitoes

描述（由申请人提供）：蚊媒寄生虫病是世界上主要的死亡和发病原因之一。最近，疟疾和登革热等蚊媒疾病的发病率急剧增加，蚊子对杀虫剂的广泛耐药性突出表明，需要采用基于蚊子特异性药剂的昆虫控制新方法。这种蚊子特异性控制剂的发现取决于对蚊子生物学的基础研究。幼体激素（JH）是昆虫体内主要的激素调节因子。在雌蚊中，JH标志着完成了向成虫阶段的蜕化，并开始了生殖过程。JH滴度主要由配体（CA）合成JH的速率决定。反过来，CA活性的速率是由同化调节肽调节的，这些肽发挥同化（抑制）或同化（刺激）活性。在该项目的前三年，我们描述了allatotropin （AT）刺激和allatostatin-C （AS-C）抑制JH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合成的激活和调节至关重要。这些肽的合成和释放与营养信号有关。因此，JH是将营养状况的变化与生殖过程中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。该项目的目标是了解肽如何调节蚊子体内JH的合成。该项目的最终目的是揭示如何评估蚊子营养状况的变化，以及如何将这些信息转导到CA。为了测试该模型，在本应用程序中，我们提出：1。探讨了AT和AS-C对JH合成的控制机理。2. 研究脑内AT和AS-C合成和释放的营养调节。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.