Neuropeptide Control of Ecdysone Biosynthesis

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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.