Regulation of Juvenile Hormone levels in mosquitos

描述(申请人提供)：由蚊子传播的寄生虫 疾病是世界上死亡和发病的主要原因之一。 最近蚊子传播疾病的发病率急剧上升 强调需要以蚊子为基础的新的虫害控制方法 特定的代理。这种蚊子特异剂的发现依赖于 蚊子生物学的基础研究。然而，有一个严重的 我们对蚊子生物学的几乎所有方面都缺乏了解。 保幼激素(JH)是昆虫体内重要的激素调节剂。成年女性 蚊子JH发出蜕皮到成虫阶段的信号，并且 生殖过程应该开始，诱导同时变化的 多种基因在卵巢、脂肪体和中肠组织中的表达。我们已经展示了 JH在早期转录激活中起重要作用 埃及伊蚊中肠中的胰蛋白酶基因。早期的胰酶是 可标记的分子标记，其表达被戏剧性地修改 摄食，它受荷尔蒙和营养的影响。我们建议使用 早期胰酶基因的表达作为营养研究的范例 对喷气式飞机水平的监管。这个项目的最终目标是了解 如何评估营养状况的变化，这些信息是 被转换为协调喂食后的生理。在这项提案中，我们是 关注JH水平的营养调节。我们的假设是 中肠可以检测喂养后的营养状况，并调节JR 通过影响舌体(CA)的活动来影响水平。这项规定 可以直接或间接地介导由 内分泌细胞并释放到血淋巴中。我们已经建立了一个分支机构 用此法测定CA合成JH的体外放射化学方法 实验表明，中肠肽提取物可促进JET的合成 埃及伊蚊促肾上腺皮质激素刺激细胞合成 加利福尼亚州的喷气式飞机。为了定义血液中JR水平是如何调节的 餐饮，提出以下具体目标：(1)调查 埃及伊蚊促生长素和他汀类药物对CA的调节作用 体外活性鉴定，(2)鉴定负责的多肽(S) 中肠排泄物调节活性及(3)探讨其生理作用 “体内”的丙二醛调节多肽。

DESCRIPTION (provided by the 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 underscore the need for new approaches to insect control based on mosquito specific agents. The discovery of such mosquito-specific agents depends on basicresearch on the biology of mosquitoes. However, there is a serious deficiency in our understanding of nearly all aspects of mosquito biology. Juvenile Hormone (JH) is amajor hormonal regulator in insects. In adult female mosquito JH signals that ecdysis to the adult stage is complete and reproductive processes should begin, inducing simultaneous changes in the expression of many genes in ovarian, fat body and midgut tissues. We have shown that JH plays an essential role in the transcriptionalactivation of the early trypsin gene in the Aedes aegypti midgut. The early trypsin is aremarkable"molecular marker," its expression is dramatically modified after feeding, and it is affected by both hormones and nutrients. We propose to use the expression of theearly trypsin gene as a paradigm for the nutritional regulation of JET levels. The ultimate goal of this project is to understand how changes in the nutritional status are assessed, and this information is transduced to coordinate post-feeding physiology. In this proposal, we are focusing on thenutritional regulation of JH levels. Our hypothesis is that the midgut can detect the nutritional status after feeding, and regulates the JR levels by affecting the activity of the corpora allata (CA). This regulation could be mediated directly or indirectly bymidgut peptides synthesized by the endocrine cells and released into the hemolymph. We have established an in vitro radiochemical assay to measure the synthesis of JH by the CA, using this assay we have shown that midgut peptide extracts stimulate thesynthesis of JET by the CA, and also that an Aedes aegyptiallatotropin stimulatesthesynthesis of JET by the CA. In order to define how JR levels are regulated after a blood meal, the following specific aims are proposed: (1) To investigate the role of the Aedes aegypti allatotropin and allatostatins on the regulation of CA activity in vitro, (2) To identify identify the peptide(s) responsible for the midgut allato-regulatory activity and (3) To investigate the physiological role of allato-regulatory peptides "in vivo."