Food intake is regulated by numerous brain structures, particularly within the hypothalamus. One hypothalamic structure, the dorsomedial nucleus (DMN), is known to regulate food intake. A recently described neuropeptide in birds, gonadotropin inhibitory hormone (GnIH), inhibits reproduction and stimulates food intake. In mammals, a related neuropeptide has been described in the DMN and identified as GnIH-3. GnIH-3 shows a strong effect to increase food intake in rats. Little to no attention has been given to the neural mechanisms underlying GnIH-3's effects on food intake. In rats, central treatment of GnIH-3 increases hypothalamic neuropeptide Y (NPY) and growth hormone releasing hormone mRNAs. Increased NPY is known to stimulate food intake. It is not known, however, if GnIH-3 increases NPY directly or if it increases NPY via increased levels of circulating growth hormone (GH);nor is it known if GnIH-3 stimulates other hypothalamic neuropeptides that regulate food intake. Thus the objectives of this application are first to determine the phenotype of neurons that are downstream targets of GnIH-3. Second, this application seeks to determine if GnIH-3 has the potential to act directly upon NPY neurons by deducing if NPY neurons co-express the GnIH-3 receptor. Third, this study will determine a causal link between GnIH-3- induced GH release and the increase in hypothalamic NPY mRNA. Thus the innovation of this application is that it seeks to understand the poorly understood role of GnIH-3 within the DMN to regulate food intake. GnIH-3's effects on food intake are described in every species examined, but the neural circuitry that modulates this effect has, as yet, not been investigated. The broader scope of this application lies in the training of undergraduate students. The proposed experiments combine behavioral, surgical, histological, anatomical, and molecular biological techniques. This combination of techniques illustrates to trainees the interdisciplinary aspects to neuroscience and helps prepare them for post-baccalaureate education. Furthermore, Hope College's mission towards """"""""Teaching Through Hands-on Research"""""""" gives my students an opportunity to be in the laboratory, to perform research, to write scientific papers and to present data at national meetings. Students even have the opportunity to do a small amount of teaching if desired. The majority of students in my laboratory over the last 7 years have been women and/or from under-represented groups.

Public Health Relevance

Many diseases that affect reproduction also have effects on eating behaviors;and, many diseases that alter eating behaviors also effect reproduction. The dual control over both feeding and reproduction occurs in the brain, however, exactly how the brain controls both feeding and reproduction is poorly understood. This application seeks to more fully understand brain circuits and the proteins used by these circuits to render dual control over feeding and reproduction.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Academic Research Enhancement Awards (AREA) (R15)
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Special Emphasis Panel (ZRG1-MDCN-A (96))
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Hyde, James F
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Hope College
Schools of Arts and Sciences
United States
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