The overall objective of this project is to determine the physiologic role of somatomedin-C (Sm-C) and other circulating forms of somatomedin in the regulation of growth. Specifically, we will clone and sequence the gene for the somatomedin-C precursor in order to study the mechanisms involved in the biosynthesis of somatomedin-C and the subsequent processing of the gene product. These studies will be carried out in human tumor cell lines which we have identified as producers of somatomedin-C-like activity. We will use the monoclonal antibodies which we have obtained against somatomedin-C production or storage. We will passively immunize young animals with these antibodies to determine the role of somatomedin-C in growth. The contributions of somatomedin-C to the mitogenic activity of serum will also be identified by immunoneutralization. We will continue to fractionate large quantities of human plasma to produce somatomedin-C, IFG-II, and related substances. We will determine the role of somatomedin-C in the feedback mechanisms controlling the secretion of growth hormone and other pituitary hormones and the mechanisms by which somatomedin-C interacts with other peptide growth factors in regulating cell replication.
