Polypeptides synthesized in the hypothalamus have been implicated in the control of hypophysiotrophic hormone release by the anterior pituitary. Recent evidence, however, has shown unequivocally that these polypeptides, referred to as releasing hormones or factors, have significant extrahypophyseal activity that is independent of their effect on the adenohypophysis. These observations have prompted speculation that the polypeptides, and particularly thyrotropin-releasing factor (TRF), in fact may be brain neuroregulatory agents. Preliminary data obtained in our laboratory is in accord with this hypothesis, and specifically suggests that TRF modulates activity of dopamine-beta-hydroxylase. Research outlined in this proposal will evaluate the regulatory role of TRF in brain, and the specific modification of catecholamine metabolism. Evaluation of the effects on catecholamine function will include potential interactions of TRF on isolated portions of metabolic pathways, including uptake, synthesis and degradation. These studies will serve as a preface to analysis of similar effects in living animals. The second portion of the proposal will proceed independently. We reason that if TRF is a neuroregulatory agent then it should possess metabolic characteristics similar to those of known neuroregulatory compounds. Thus, we will define the chemical distribution (anatomic as well as subcellular), the nature and localization of enzymes controlling its synthesis and degradation, and possible mechanisms responsible for its transport and storage in cells.