This proposal is designed to study the form of calcitonin which we have recently discovered in the pituitary gland of the rat, the chicken, the fish, and five other animal species. We shall perform systematic studies of pituitary calcitonin in the rat, chicken, and fish. The rat serves as a model for mammals which contain classical calcitonin-secreting cells (C-cells) in the thyroid gland. The fish and chicken serve as prototypes for submammals which contain C-cells in the ultimobranchial gland. In addition to these species, we shall perform selected studies of pituitary calcitonin in some of the other animal species such as the sheep, pig, cow, and human. The distribution of calcitonin in the pituitary and brain will be determined by immunohistology and immunoassay. The immunochemical form(s) of pituitary (and brain) calcitonin and its relationship to other pituitary (and brain) peptides will be determined by immunoassay and molecular sizing studies. In vivo and in vitro secretion studies will be conducted to define the factors which regulate pituitary calcitonin. Biochemical and bioassay studies will be performed on some species of pituitary calcitonin. The studies will be performed for each of the animal species of calcitonin by sensitive and specific radioimmunoassay, bioassay, immunohistology, biochemical and immunochemical procedures which we have developed in our laboratory. This proposal should help to define the physiological significance of pituitary calcitonin and to establish its relationship to thyroidal and ultimobranchial calcitonin and to other pituitary and brain peptides.