Synthesis and Circulating Forms of The Somatomedins

Abstract

Our data support the hypothesis that the somatomedins have multiple origins and may have paracrine and autocrine as well as humoral modes of action. The balance between the local actions and hormoral actions of somatomedin in any physiologic circumstance remains to be determined by future experiments. We have also found evidence that the initial products of IGF secretion synthesis include a carboxyterminal E region extension as predicted by the messenger RNA structure. In normal circumstances, the E region appears to be rapidly and efficiently cleaved. However, in certain metabolic conditions IGF-I prohormone is found in the circulation. Our initial characterization of the circulating IGF-I prohormone suggests that the prohormone form of IGF is unable to bind to either the type IGF receptor or to the binding proteins. In addition, we have demonstrated that normal plasma contains an active and specific peptidase for the E region, which is associated with molecules of the 150, 000 molecular weight range in plasma. A small binding protein for somatomedin has been isolated from a number of human sources and partial sequence data has been reported. There is at least some immunological and structural homology between the binding protein associated with the 150, 000 micro-weight complex and the small somatomedin binding protein. Biological regulation of somatomedin synthesis and action can occur at multiple sites, including messenger RNA synthesis, prohormone synthesis and processing, and incorporation into mature somatomedin complexes in plasma. The biological control of these processes, and their relationship to the biological actions of the somatomedins, will be a source of fruitful future study.