Neuropeptide Control of Ecdysone Biosynthesis

昆虫的前胸腺合成和分泌一类被称为蜕皮激素的类固醇激素，正是这些蜕皮激素导致细胞重新编程并引发蜕皮(合成新的外骨骼，使昆虫能够生长)。因此，对前胸腺活动的控制有助于昆虫在这个星球上的成功，这种控制的主要调节成分是昆虫大脑分泌的一种神经肽，促胸腺激素(PTTH)，它刺激前胸腺合成和分泌蜕皮激素。这个项目的目的是在细胞和生化水平上确定这种多肽激素如何作用于前胸腺，导致蜕皮类固醇的合成。到目前为止，主要研究人员的工作表明，PTTH对前胸腺的作用与脊椎动物ACTH对肾上腺的作用非常相似。也就是说，这种多肽作用于腺体表面，引起一种特定的酶，腺苷环化酶的激活，导致腺体细胞内第二信使分子环磷酸腺苷(CAMP)的增加。环状AMP反过来激活被称为蛋白激酶的特定酶，这种酶有能力将磷酸盐添加到其他蛋白质中，从而“激活”这些蛋白质。他们的计划是识别被激活的蛋白质，并确定它们在蜕皮激素生物合成中的调节作用。此外，研究人员打算进一步研究钙在腺苷环化酶激活中的作用，以确定甲状旁腺激素是否通过打开细胞膜上的通道作用于前胸腺细胞，即钙通道，以及细胞内的钙-钙调蛋白系统是否直接影响腺苷环化酶。这些研究对包括人类在内的所有动物都有意义，因为PTTH-前胸腺轴和ACTH-肾上腺皮质轴非常相似。此外，昆虫是地球上最普遍的动物生命形式，显然，人们应该从学术角度更多地了解这些非常成功的有机体，因为有了这些信息，他们可能能够设计出更好的方法来控制有害昆虫。昆虫作为疾病的传播者和农产品的破坏者是非常重要的。通过干扰昆虫的蜕皮过程，理论上可以控制特定的昆虫种群。

The prothoracic glands of insects synthesize and secrete a class of steroidal hormones known as ecdysteroids and it is these ecdysteroids that cause cellular reprogramming and elicit molting (synthesis of a new exoskeleton so that the insect can grow). The control of prothoracic gland activity, therefore, is instrumental in the success of insects on this planet and the main regulatory component for this control is a neuropeptide secreted by the brain of the insect, prothoracicotropic hormone (PTTH) which stimulates the prothoracic glands to synthesize and secrete ecdysteroids. The aim of this project is to determine at the cellular and biochemical levels how this peptide hormone acts on the prothoracic gland to cause the synthesis of ecdysteroids. The principal investigators' work thus far indicates that the action of PTTH on the prothoracic glands is quite similar to the action of the vertebrate ACTH on the adrenal glands. That is, the peptide acts at the surface of the gland causing the activation of a specific enzyme, adenylate cyclase, causing an increase within the cells of the gland of a second messenger molecule, cyclic AMP (cAMP). The cyclic AMP, in turn, activates specific enzymes known as protein kinases which have the ability to add a phosphate to other proteins and thus "activate" these proteins. It is their plan to identify the proteins that are activated and determine their regulatory role in ecdysteroid biosynthesis. In addition, the investigators intend to examine further the role of calcium in the activation of the adenylate cyclase to determine whether PTTH acts on the prothoracic gland cell by opening a channel through the membrane of the cell, the calcium channel, and that it is the calcium-calmodulin system within the cell that directly affects the adenylate cyclase. These studies have significance for all animals including man because of the close analogy between the PTTH-prothoracic gland axis and the ACTH-adrenal cortex axis. In addition, insects are the most prevalent form of animal life on this planet and it is obvious that one should learn more about these very successful organisms from an academic point of view and because with such information they may be able to design better means for controlling harmful insects. Insects are of great importance as vectors of disease and as devastators of agricultural products. By interfering with the insect's molting process, one could theoretically control specific insect populations.