9720633 Olster The energetic costs of reproduction for a female mammal are enormous. Thus, it is not surprising that in many animals, reproduction is influenced by factors related to energy balance, such as food intake, body weight, energy expenditure, and metabolism. Animals that are undernourished or obese often suffer from reproductive abnormalities. The experiments described by Dr. Olster will use the genetically obese Zucker rat to explore the interaction between obesity and abnormal reproductive function. Females of this strain overeat, expend less energy than normal and are obese. These animals exhibit many other abnormalities, including overproduction of insulin and corticosterone (hormones related to the use and storage of nutrients obtained from the diet), insulin resistance, and higher than normal concentrations of neuropeptide Y, a hypothalamic neurochemical that stimulates food intake. Finally, obese Zucker females are infertile. Previous research from this laboratory has demonstrated that these animals have delayed puberty, do not ovulate regularly, and show minimal mating behavior with males. When normal (i.e., lean) rats are experimentally given extra neuropeptide Y, they exhibit a syndrome that is very similar to the abnormal metabolic and reproductive physiology of obese Zucker rats, namely overeating, obesity, oversecretion of insulin and corticosterone, insulin resistance, aberrant reproductive cyclicity and impaired sexual behaviors. The experiments in this proposal are designed to explore the roles of neuropeptide Y, insulin and corticosterone in reproductive dysfunction in obese Zucker rats, with an emphasis on sexual behaviors. These substances will be experimentally manipulated in an effort to improve the reproductive capacity of obese Zucker rats and/or induce reproductive abnormalities in lean females. The knowledge gained from these studies will provide new, exciting information about the signals (of brain, endocrine and/or metabolic origin) that convey i nformation regarding energy balance to the systems regulating reproduction. This cross-talk is of critical importance in allowing animals to reproduce only when it is energetically appropriate to do so.
