The objectives of this research include a comprehensive study of the mechanisms of differentiation and development and the action of thyroid hormone using amphibian metamorphosis as a model system. Particular attention is paid to the initiating mechanisms by which thyroid hormones trigger the metamorphic process. Many basis facets of protein and nucleic acid biosynthesis are involved. We also hope to contribute to knowledge of comparative biochemistry, embryonic development and biochemical evolution. In this broad field, emphasis will be placed on seven major objectives: (1) The development of viable amphibian cell cultures to study the effect of hormones, particularly thyroid hormones, on intact cells, e.g. the liver, kidneys, and other tadpole tissues. (2) Studies on the changes in DNA and RNA biosynthesis in spontaneous and induced metamorphosis in numerous tissues. (3) Protein biosynthesis in liver and other anabolic tissues with particular reference to changes in nuclear and mitochondrial proteins. (4) A study of the ability of tadpole serum and tissue proteins to bind T3 and T4 and to relate this binding to hormone function in tadpoles. (5) Metabolism of regressing tissues, particularly in relation to the activities of particular cells which may be be responsible for the increase in hydrolytic activity in these tissues. (6) Further studies on metalloprotein metabolis during metamorphosis- in particular cerulplasmin, transferring and hemoglobin. (7) The possibility that additional factors, hormonal or otherwise, may be involved in at least certain responses during metamorphosis. BIBLIOGRAPHIC REFERENCES: E. Frieden, A. Kent. The Evolution of the Dual Role of the Thyroid Hormone, Int. Thyroid Conf. (1976) in press. G. VanDenbos and E. Frieden, DNA Synthesis and Turnover in the Bullfrog Tadpole During Metamorphosis. J. Biol. Chem. (1976) in press.