STEROID REGULATION OF PEPTIDE SENSITIVITY IN THE CNS

类固醇激素会导致血管形态和功能的长期变化。 神经系统。这些变化很可能是通过 基因组。这个项目的目的是利用类固醇调节一种 昆虫Manduca sexta的多肽介导的行为作为研究如何 类固醇可以控制中枢神经系统的反应。蜕皮类固醇是 调节昆虫变态和蜕皮的类固醇激素。 蜕皮过程中的最后一步是蜕皮。 旧的角质层。此行为由 神经肽，羽化激素(EH)。这种多肽只能作用于中枢神经系统， 然而，如果神经系统因暴露于 蜕皮类固醇。 我进行的研究表明，蜕皮类固醇在两个月内起作用。 或更多的水平来调节多肽的反应性。首先是关于 受体/第二信使(CGMP)系统；第二，诱导从头 两种被作用磷酸化的蛋白质(EGPS)的合成 多肽的含量。只有当这两个组件都起作用时， 神经系统对EH有反应。这项建议的目的是研究 对这两个步骤的类固醇调节都进行了详细的阐述。使用放射性标记的EH 我将确定EH受体的特征，并确定它们是否上调 对蜕皮类固醇的反应。我还将阐明EH的途径 升高cGMP，并确定该途径的任何元件是否受 蜕皮激素。 我认为从头合成EGP是 使CNS能够对EH做出反应。一旦针对EGP的抗体已经被 生成的我将能够跟随它们的合成，合成的 EGP mRNA(S)及其类固醇调节。 最终，我打算在每一步中分离类固醇调节基因 EH行动的级联效应。从这项提案中获得的信息将 对中枢神经系统可塑性的其他研究具有重要意义 在基因组水平上受到调控。

Steroid hormones induce long-term changes in the form and function of the nervous system. These changes are likely mediated via changes in the genome. The aim of this project is to use the steroid regulation of a peptide-mediated behavior of an insect, Manduca sexta, as a model for how steroids can control the responsiveness of the CNS. The ecdysteroids are steroid hormones which regulate the metamorphosis and molting of insects. One of the final steps in the molting process is the shedding (ecdysis) of the old cuticle. This behavior is triggered by the action of a neuropeptide, eclosion hormone (EH). The peptide can only act on the CNS, however, if the nervous system has been primed by exposure to the ecdysteroids. Studies that I have carried out indicate that the ecdysteroids act at two or more levels to regulate peptide responsiveness. Firstly on the receptor/2nd messenger (cGMP) system and secondly, inducing the de novo synthesis of two proteins (the EGPS) which are phosphorylated by the action of the peptide. Only when both of these components are functional will the nervous system respond to EH. The aim of this proposal is to examine the steroid regulation of both of these steps in detail. Using radiolabeled EH I will characterize the EH receptors and determine if they are up regulated in response to ecdysteroids. I will also elucidate the pathway by which EH elevates cGMP and ascertain if any element of this pathway is regulated by the ecdysteroids. I believe that the de novo synthesis of the EGPs is the final step in enabling the CNS to respond to EH. Once antibodies to the EGPs have been generated I will be able to follow their synthesis, the synthesis of the EGP mRNA(s) and their steroid regulation. Ultimately, I intend to isolate the steroid-regulated genes at each step in the cascade of EH action. The information gained from this proposal will be of importance to other studies in CNS plasticity which are believed to be regulated at the level of the genome.