This research project examines the reciprocal interactions between reproductive function and regulation of energy balance in female mammals. In females, successful reproduction requires a great deal of energy, and numerous behavioral and physiological mechanisms have evolved which link reproduction to the availability of calories. When food is scarce, or when an excessive fraction of the available energy is diverted to other uses such as exercise or thermoregulation, reproduction is suppressed in all species that have been studied, including human beings. When reproduction is attempted, changes in the circulating levels of ovarian hormones have a dramatic impact on both regulatory behaviors and metabolic controls of energy balance. Again, these ovarian effects on energy balance are seen in females of many species, including women. One line of research examines behavioral components of nutritional infertility, using female hamsters as an animal model. Food deprivation suppresses estrous behavior in hamsters, and the effects of food deprivation are mimicked by pharmacological inhibition of glucose utilization (glucoprivation) and of fatty acid oxidation (lipoprivation). Several proposed experiments will employ peripheral nerve sections, brain lesions, and selective delivery of metabolic inhibitors in order to determine where glucoprivation and lipoprivation are detected and how this information is transmitted to the neural circuits controlling female reproductive behaviors. Nutritional manipulations that inhibit estrous behavior also decrease estrogen binding in the ventromedial hypothalamus, which could be responsible for the behavioral changes. Parallel experiments will examine the neuroendocrine mechanisms by which metabolic fuels modulate neural estrogen binding. A second line of research investigates the effects of metabolic fuel availability on ovulatory cycles in hamsters. Glucoprivation alone is sufficient to suppress secretion of luteinizing hormone and prevent ovulation. Again, the proposed experiments will employ peripheral nerve sections, brain lesions, and selective delivery of metabolic inhibitors in order to determine where glucoprivation is detected and how this information is transmitted to the neurons controlling gonadotropin secretion. Glucoprivation may inhibit ovulatory cycles via gonadotropin releasing hormone (GnRH) neurons in the forebrain. Further experiments will use immunocytochemical detection of Fos, a marker of neuronal activation, to study nutritional effects on GnRH neurons. A third line of research focuses on the effects of the ovarian steroids, estradiol and progesterone, on behavioral and physiological controls of energy balance and body weight regulation using rats and hamsters as experimental subjects. One group of experiments will explore the effects of progesterone on regulatory behaviors and metabolism. Another group will examine the possibility that estradiol and progesterone act in the brain to alter autonomic activity and, consequently metabolism of metabolic fuels.
