Neuropeptide Control of Ecdysone Biosynthesis

9603710吉尔伯特这些研究集中在昆虫大脑中的激素如何作用于专门的腺体(前胸腺)，使这些腺体合成一种特定的类固醇激素，一种蜕皮激素。蜕皮类固醇使昆虫蜕皮，即脱下外骨骼，这样它就可以生长。这些激素还会引起变态，也就是说，毛毛虫变成蛹，然后变成成虫或蝴蝶的现象。大脑神经激素的合成和释放是环境信号的结果，前胸腺合成和释放蜕皮类固醇必须极其精确，才能使昆虫生存和成功。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法，这些事件包括被称为第二信使的化合物，即环磷酸腺苷和蛋白激酶。这些第二信使的作用是这项赠款申请的重点，到目前为止，PI所研究的机制与人类肾上腺皮质非常相似，人类肾上腺皮质受到一种垂体激素的刺激，这种激素也能引起类固醇的合成，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希望深入了解一般多肽激素诱导类固醇生成的机制，这是更多异源肾上腺所不可能实现的。此外，这两个系统之间发现的任何差异都可能被那些研究害虫控制的人所利用，这些害虫对人类的健康和营养造成了如此不利的影响。

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.