In female mammals, reproduction is extremely sensitive to the availability of oxidizable metabolic fuels. When food intake is limited or when an inordinate fraction of the available energy is diverted to other uses such as exercise, reproductive attempts are suspended in favor of processes necessary for individual survival, resulting in nutritional infertility. Both reproductive physiology and sexual behaviors are influenced by metabolic fuel availability. Work using pharmacological inhibitors of glucose and fatty acid oxidation indicates that reproductive physiology and behaviors respond to short-term (minute-to-minute or hour-to-hour) changes in metabolic fuel oxidation, rather than to any aspect of body size or composition (e.g., body fat content or fat-to-lean ratio). These metabolic cues seem to be detected in the viscera (most likely in the liver) and in the caudal hindbrain (probably in the area postrema). This metabolic information is then transmitted to effector neurons in the forebrain. This metabolic fuels hypothesis is consistent with a large body of evidence and seems to account for the infertility that is seen in a number of situations, including famine, eating disorders, excessive exercise, cold exposure, lactation, some types of obesity, and poorly controlled diabetes mellitus. The experiments proposed in this application focus on the physiological processes mediating deficits in female reproductive behaviors that are seen in nutritional infertility. The first group of experiments examines the role of the paraventricular nucleus of the hypothalamus on nutritional control of estrous behavior. A second group of experiments is directed at determining how information about metabolic fuel tvailability is transmitted from the putative detectors to forebrain effector cells, focusing on the neurotransmitter/neuropeptide systems involved. A third proposed line of research examines the effects of metabolic fuel availability on matern',_ behavior in hamsters.
