IGFs

Insulin-like growth factors (IGFs) are a family of peptide hormones with structural similarity to insulin, essential for normal growth and development. The primary members are IGF-1 and IGF-2, which operate within an intricate system that also includes several IGF binding proteins (IGFBP-1 to IGFBP-6) and receptors that mediate signaling. The IGF system regulates the availability, distribution, and activity of IGFs in tissues.

IGF-1 is produced mainly by the liver in response to growth hormone (GH) and transmits many of GH’s growth-promoting effects. IGF-2 is produced in multiple tissues and plays a crucial role in fetal development, with its expression largely independent of GH during early life. IGFBPs modulate IGF actions by extending half-life, restricting receptor access, or delivering IGFs to specific tissues.

Receptors and signaling: IGF-1 receptor (IGF-1R) is a receptor tyrosine kinase that, when bound by IGF-1 or IGF-2, activates signaling cascades such as the PI3K-AKT and MAPK pathways, promoting cell proliferation, differentiation, and survival. The IGF-2 receptor (IGF-2R, also known as the mannose-6-phosphate receptor) primarily regulates IGF-2 availability by directing it for degradation rather than signaling.

Functions: IGFs regulate embryonic and postnatal growth, bone remodeling, muscle development, metabolism, and organ maturation. In adults, they contribute to tissue maintenance and can influence insulin sensitivity in certain contexts.

Clinical relevance: Altered IGF signaling associates with growth disorders (low IGF-1 in GH deficiency; high IGF-1 in conditions like acromegaly) and cancer biology (IGF-2 overexpression in some tumors). IGF-1 measurement aids GH axis assessment; recombinant IGF-1 is used therapeutically for specific growth deficiencies, while IGF-1R inhibitors and related strategies are studied in oncology.