9319653 Bittman All Multicellular organisms possess an internal clock that insures daily rhythmicity of multiple physiological function even in an aperiodic environment. In higher vertebrates, these endogenous daily or circadian rhythms are driven by the suprachiasmatic nucleus of the hypothalamus. This endogenous oscillator insures that incompatible processes occur at different times, and that metabolic, thermoregulatory, osmoregulatory, immune and reproductive functions and arousal are properly scheduled to meet environmental challenges. Dr. Bittman will elucidate the role of this central pacemaker in the timing of ovulation. Ovulation is triggered by a surge of pituitary luteinizing hormone which results from the discharge in tot he hypothalamic-hypophyseal portal system of gonadotropin releasing hormone, a decapeptide synthesized in cells of the diagonal band, medial septum, preoptic area and anterior hypothalamus. This release of gonadotropin-releasing hormone is ultimately regulated by estrogen. Dr. Bittman will examine the function of specific cell types within the suprachiasmatic nucleus in the regulation of the estrous cycle by determining whether these neurons project directly to cells elsewhere in the brain which in turn control the pituitary gland. Using state-of-the-art neuroanatomical techniques, Dr. Bittman will then determine whether these neurons that receive input from this hypothalamic nucleus contain estrogen receptor or gonadotropin releasing hormone. In addition, he will establish whether the signals from the suprachiasmatic nucleus at specific times of day underly the appropriate timing of ovulation. The results from these studies will help delineate the circadian regulation of neuroendocrine cells which govern integrative processes. This research will provide basic information critical not only to understanding how environmental factors impinge upon the nervous system but may provide the fundamental groundwork towards developme nt of therapeutic approaches to fertility and may have applications to contraception. ***
