Peptide hormones are chemical signals that are secreted by cells to control the functioning of the brain and many other tissues. They are key regulators of diverse processes, including growth, reproduction, stress, sleep, body weight, pain, and daily rhythms. The long-term goal of this proposal is to understand the mechanisms within cells that underlie the regulation of peptide hormone signaling by steroids. Specifically, this work will define mechanisms underlying the steroid regulation of the gene encoding the peptide hormone, ecdysis-triggering hormone (ETH). Toward this end, methods were established in the fruit fly, Drosophila melanogaster, for manipulation of steroid signaling in single cells. This is combined with tracking of ETH gene expression through genetic and molecular assays, and genetic manipulations to measure the contributions to this process from steroid receptors and other interacting proteins. The cellular sites of steroid receptor action underlying the regulation of ETH gene expression, and the roles of different DNA sequences within the ETH gene, will be determined genetically and biochemically. The regulation of gene expression by steroid receptors requires the participation of co-factors. These will be identified through genetic screens. Together, these experiments will examine how co-factors for a steroid receptor can mediate cell-type specific expression of steroid hormone-responsive genes. This basic research will contribute to our understanding of the disruptions in hormone signaling associated with human diseases, such as obesity, diabetes and cancer. This work will also be a unique opportunity for several undergraduate and graduate students to participate in research. Students in Oklahoma have few options for non-agricultural training in the sciences. The experiences provided by this project are not otherwise readily available, and they complement traditional lecture-format courses. These research experiences will continue to enable and inspire talented students from the State of Oklahoma to pursue professional careers in industry, medicine, and scientific research.
