The purpose of this research is the elucidation of the biochemical processes responsible for the homeostasis of proteins in connective tissue. The mechanism of protein synthesis has been described and circumstantial evidence is available that protein synthesis and protein degradation are synchronized by some control mechanism. Investigations concentrating on the catabolic aspect of protein metabolism have been hampered by the inavailability of any information concerning the mechanism by which proteins are degraded or selected for degradation. A multiple attack on this problem is proposed. An intensive search for neutral proteases (endopeptidases) will be undertaken with the aid of endogenous and exogenous, natural and synthetic radioactive substrates. In addition surviving connective tissue slices will be subjected to a great number of conditions designed to induce intracellular protein breakdown. Such a system should enhance the chances to find enzymes that might be inhibited under physiological conditions as well as to find breakdown products of the action of such proteases. As a final approach the hormone relaxin will be purified and its sequence determined. Using the chemically defined hormone or hormone containing radioactive substitutions, attempts will be made to investigate the mode by which relaxin either increases the synthesis of collagen and protein-polysaccharides or inhibits their degradation. Through these studies we hope to come closer to an understanding of the processes occurring in connective tissue during degenerative changes, such as the premature loss of dentition supporting structures or the degeneration of joints. Degenerative changes which may or may not be exaggerated by inflammatory complications are visualized as a disorder involving the "protein cycle"; that is the synchronization between the synthetic and the degradative branches of protein metabolism. It seems therefore extremely important to learn about the mechanisms that synchronize the two processes in vivo.