Neuropeptide Control of Ecdysone Biosynthesis

这些研究集中在昆虫大脑中的激素如何作用于特定的腺体（前胸腺），使这些腺体合成一种特定的类固醇激素，一种外皮类固醇。蜕皮激素使昆虫蜕皮，即脱落外骨骼，以便生长。这些激素还会引起变态，即毛毛虫从蛹变成成虫蛾或蝴蝶的现象。如果昆虫想要生存和成功，那么由于环境因素而合成和释放的脑神经激素和前胸腺的外甾体激素的合成和释放必须非常精确。这笔拨款将允许PI研究这种肽激素通过一系列事件与前胸腺相互作用的方式，包括被称为第二信使的化合物，即环AMP和蛋白激酶。这些第二信使的作用是本次拨款申请的重点，迄今为止，PI研究的机制与人类肾上腺皮质非常相似，肾上腺皮质受到垂体激素的刺激，也会引起类固醇的合成，即皮质类固醇。通过利用由单层同质细胞组成的昆虫前胸腺，PI希望能够深入了解一般肽激素诱导的类固醇生成机制，而这是异质肾上腺无法实现的。此外，这两种系统之间发现的任何差异都可以被那些研究如何控制对人类健康和营养造成不利影响的害虫的人所利用。

9603710 Gilbert These studies concentrate on the means by which a hormone from the insect brain acts upon specialized glands (prothoracic glands) to cause these glands to synthesize a specific steroid hormone, an ecdysteroid. Ecdysteroids cause the insect to molt i.e. shed its exoskeleton, so that it can grow. These hormones also elicit metamorphosis i.e. the phenomenon by which a caterpillar is transformed into a pupa and then into an adult moth or butterfly. The brain neurohormone that is synthesized and released as a result of environmental cues and the synthesis and release of ecdysteroids by the prothoracic glands must be extremely precise if the insect is to survive and be successful. This grant will allow the PI to study the means by which this peptide hormone interacts with the prothoracic glands via a cascade of events that includes compounds known as second messengers i.e. cyclic AMP and protein kinases. The role of these second messengers is the focus of this grant application and the mechanisms the PI has thus far examined are very similar to that of the human adrenal cortex which is stimulated by a pituitary hormone that also elicits the synthesis of steroids i.e. corticosteroids. By utilizing the insect prothoracic glands which are composed of a single layer of homogenous cells, the PI hopes to gain insights into the mechanism of general peptide hormone induced steroidogenesis that would not be possible with the more heterogenous adrenal gland. Further, any differences found between the two systems could be exploited by those studying the control of insect pests which so adversely affect human health and nutrition.