The specific aim of this Program Project is to carry out a detailed analysis of the relationship between the structure of growth hormone and its growth-promoting activity in order to define the minimum structure required for activity in man. Human growth hormone will be subjected to partial degradation by enzymes and by other chemical reagents. In each instance, the nature and chemical characteristics of the fragments produced will be established. The biological characterization of these fragments of growth hormone will then be carried out using a battery of animal assays which will yield information about anabolic activity, insulin-like activity and diabetogenic activity. This will permit an analysis of the relationship of these various activities to structure of the hormone molecule and their relationship to each other. The fragments that show significant activity in the animal assays will then be tested for metabolic activity in human subjects. Hopefully, these studies will lead to the identification of the minimum structure of the growth hormone molecule required for growth-promoting activity in animals and man. Once this minimum structure is identified, it may be possible, if it is reasonably small, to produce it synthetically. BIBLIOGRAPHIC REFERENCES: Reagan, C.R., Mills, J.B., Kostyo, J.L., and Wilhelmi, A.E. Biological activity of plasmin digests of S-carbamidomethylated human growth hormone. Proc. Nat. Acad. Sci. (USA) 72: 1684-1686, 1975. Mills, J.B., Zeringue, M., Harris, R., Wilhelmi, A.E., and Rudman, D. Assay of pig growth hormone preparations for metabolic activities in the rat and man. J. Clin. Endocrinol. Metab. (in press).