The discovery of insulin-like growth factors (IGFs) began in 1957 when Salmon and Daughaday observed that the serum from pituitary-removed rats stimulated cartilage cells to incorporate sulfate, but this effect was not due to growth hormone (GH). Instead, they proposed the existence of a "sulfation factor," later named the growth regulator. In 1963, Froesch et al. identified a non-suppressible insulin-like activity (NSILA) in serum, which was resistant to insulin antiserum and could be precipitated with acidified ethanol. By 1972, Pieron and Temin isolated a factor called "proliferative stimulating activity" from bovine serum. With advances in molecular biology, NSILA was later identified as IGF-I and IGF-II, showing structural similarities to proinsulin.
IGF family consists of two peptides (IGF-I and IGF-II), two specific receptors, and six binding proteins. IGF-I is a 70-amino acid basic protein with a molecular weight of 7649 Da, while IGF-II is a 67-amino acid weakly acidic protein weighing 7471 Da. Both share about 70% homology and are structurally similar to human proinsulin. Their biological effects are mediated through IGF-I and IGF-II receptors, which differ in structure and ligand specificity. IGFs bind to IGFBPs, forming complexes that regulate their bioavailability and half-life.
IGFs play a critical role in fetal development, with IGF-I dependent on GH for cell proliferation and protein synthesis, while IGF-II is primarily active before birth. Studies show that IGF-II is essential for trophoblast invasion and early implantation, while IGF-I increases during pregnancy. Genetic studies reveal that mice lacking IGF-I or IGF-II exhibit severe growth defects, highlighting their importance in embryonic and postnatal development.
Research into IGFs continues to uncover their roles in growth, metabolism, and disease. They have potential therapeutic applications, especially in conditions like GH insensitivity. Ongoing studies aim to better understand their mechanisms and interactions within the body.
References:
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