Insulin-like Growth Factor I and its Binding Proteins in Health, Aging and Disease

The insulin-like growth factors (IGFs) were discovered in 1956 by William D. Salmon Jr. and William H. Daughaday at Washington University, St Louis, USA. Initially IGFs were called sulfation factors because they were able to replace the sulfation factor activity of growth hormone (GH)(l). Moreover, the IGFs were found to be able to stimulate DNA synthesis , proteoglycan synthesis, glycosaminoglycan synthesis, and protein synthesis. In 1963 Froesch et al. from the University of Zurich, Switzerland, described excess insulin-like activity in serum. Only a small fraction of the insulin-like activity by normal serum on adipose tissue and muscle could be blocked by specific antibodies against insulin. The mediator of this excess insulin-like activity was not detectable with the radioimmunoassay developed for insulin in 1959, and was termed non-suppressible insulin-like activity (NSILA). Dulak and Temin demonstrated that serum-free medium conditioned by a rat hepatoma cell line contained mitogenic activity, which they termed multiplicationstimulating activity (MSA). In 1972 these three apparently distinct peptides (sulfation factor, NSILA, MSA) were unified under the term somatomedin, because it apparently mediated the actions of GH (also called somatotropin). In 1978 Rinderknecht and Humbel purified somatomedin from serum, and it turned out to be two closely related peptides, which were termed Insulin-like growth factor-I (IGF-I) and Insulin-like growth factor-II (IGF-II).