The broad objective of the proposed research is to investigate cellular interactions of thyroid hormone molecules relevant to their effects on growth, development, and metabolism. We have previously suggested, and have provided experimental support for the concept that an amino acid function of the iodothyronines, namely theri ability to be incoporated into proteins of developing organisms, may account for their effects on growth and differentiation. In the present proposal we are suggesting that the iodothyronines may function as precursor amino acids in the catecholamine biosynthetic pathway, leading to the development of metabolites which might influence overall energy transformations of the organism. In collaboration with Dr. Julius Axelrod, we propose to study the metabolism of ringlabelled as well as iodine-labelled thyroxin following pharmacologic alteration of adrenergic nervous system activity. The first of these experiments has been completed and results are documented in the body of the application. In parallel with the pharmacologic experiments, analogous to those derived from tyrosine, in the pathway leading to the adrenergic neurotransmitter substances. These derivatives will serve as model compounds in the required biochemical analytic procedures. The biologic potency of these compounds with regard to their influence on adrenergic mechanisms will be tested in collaboration with Dr. John R. Vane.