Reproduction, Nutrition and Behavior

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DESCRIPTION (provided by applicant): Reproductive behaviors are typical of a variety of motivated behaviors that require integration of multiple internal and external cues for their successful execution. Gonadotropin releasing hormone (GnRH) is a master neuropeptide that coordinates reproductive condition and behavior. Yet, many animals, including humans, have a second form of GnRH, GnRH-II, which is highly conserved, present in brains of animals from all vertebrate classes (bony fish to humans), produced by a unique group of neurons and yet the peptide has no known function. In this new application we will test the novel hypothesis that this neuropeptide, GnRH-II, modulates reproductive behavior in response to the individual's nutritional status. Our hypothesis is based on our findings that; 1) Intracerebroventricular (icv) administration of GnRH-II, but not GnRH-I, peptide activates reproductive behavior in female musk shrews (Suncus murinus), but only in females experiencing caloric restriction; 2) Immunoreactivity of GnRH-II peptide varies with reproductive condition and nutritional status in female musk shrew brains, 3) Musk shrew brains contain specific type-II GnRH receptors which have a high affinity for GnRH-II peptide, and these receptors are found in nuclei known to control reproductive behavior, and 4) GnRH-II infusions suppress food consumption. In our laboratory we have the needed resources, experience with this animal model, and technical expertise to conduct these studies. We will use a combination of pharmacology, immunocytochemistry, surgical, and behavioral methods to build this new research program. The work proposed here will elucidate the function of GnRH-II in a novel and highly appropriate mammalian model system. The presence of the GnRH-II peptide in rodent brain is unclear, yet this peptide is widespread in human and non-human primates. By examining this neuropeptide first in a primitive mammal we will reveal the conserved and likely the most common function of this neuropeptide. This work employs several novel approaches to dissect the relationship between GnRH-II, feeding and sexual behaviors, and nutrition. It is likely that this information will provide new approaches for the study of GnRH-II peptide in humans. Moreover, this work may provide insights into physiological bases of eating disorders.