Endocrine Index Glossary
Insulin-like Growth Factors: IGF-I and IGF-II
Insulin-like growth factors or IGFs are peptide hormones secreted from many different cells. Their designation as "insulin-like" originated from experiments in which treatment of serum with antibodies to insulin failed to eliminate all insulin activity; the remaining activity was ultimately ascribed to the IGFs. Due to their growth promoting activity, they were formerly called somatomedins.
IGFs, IGF Receptors and IGF-Binding Proteins
There are two principle IGFs referred to as IGF-I and IGF-II. Each of these has a number of variant forms, resulting from use of alternative gene promoters and alternative splicing. Structurally, both IGFs resemble insulin in having two chains (A and B) connected by disulfide bonds. Human IGF-I and IGF-II are, respectively, 70 and 67 amino acids in length.
In addition to two IGFs, there are three receptors that bind IGFs with differing affinities:
- Type 1 IGF receptor: binds both IGF-I and IGF-II with high affinity. This receptor has been identified in essentially all tissues except liver, and virtually all of the biological activities of the IGFs result from binding to the type 1 receptor.
- Type 2 IGF receptor: binds IGF-II with high affinity and IGF-I with low affinity. It appears primarily to be involved in clearance and degradation of IGF-II, although it may also elicit some distinct signalling. This is also the cation-independent mannose-6-phosphate receptor used for targeting mannosylated enzymes to lysosomes.
- Insulin receptor: binds IGF-I with roughly 100-fold lower affinity than insulin. High concentrations of IGF may stimulate insulin signalling through this receptor.
Interestingly, the type 1 IGF and insulin receptors are very similar structurally. In fact, in cells that express both receptors, hybrid receptors appear to readily form, although the biological consequences of these hybrids is not clear.
A final important determinant of IGF activity is a family if IGF-binding proteins. IGFs circulate in blood complexed to these proteins, which not only extend the half-life of the hormones, but modulate their interaction with receptors. To date, at least six distinct IGF-binding proteins have been identified in humans and rats.
IGF-I: Secretion and Biological Activity
IGF-I is the hormone largely responsible for the growth-promoting properties of growth hormone.
IGF-II: Secretion and Biological Activity
Index of: Other Endocrine Tissues and Hormones
Last updated on October 8, 2004
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