Neurophysins, the intraneuronal peptides synthesized in association with oxytocin and vasopressin, have been proven to be a major secretory product of the neurohypophysis. This measure of posterior pituitary function should be applied to the study of human physiology and pathology. We have developed assays for two neurophysins in the human and demonstrated the independent secretion of each. Assays for oxytocin and vasopressin are being developed to determine if there is an "oxytocin-neurophysin" and "vasopressin-neurophysin" in man. Correlation of secretion of neurophysins and hormones will be made with physiologic maneuvers (dehydration, hypotension, parturition, suckling, etc.) with pharmacologic stimuli (ethanol, chlorpropamide, dephenylhydantoin, clofibrate, etc.) and during disease states (diabetes insipidus, inappropriate ADH syndrome, Addison's disease, myxedema, etc.). These studies will determine whether neurophysin secretion is a measure of hormone secretion. Some studies of abnormal neurophysin secretion have been suggested by preliminary studies and will be pursued. Estrogen and pregnancy cause elevation of one neurophysin in humans and this will be studied to determine if this neurophysin reflects oxytocin secretion. Possible biologic functions of neurophysins will be sought, especially the effect of estrogen stimulated neurophysin and/or oxytocin on anterior pituitary function (LH). A rat model will be used to study the effect of drugs and diseases on secretion of neurophysins and hormones. In the rat single variables can be studied. Collaborative efforts in monkeys and rats with hypothalamic lesions will correlate changes in neurohypophyseal secretion with hypothalamic damage. This is a comprehensive study of the anatomy, pathology, physiology and pathophysiology of all the known peptides which are secreted from the neurohypophysis.