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The insulin-like growth factor (IGF) family comprises two ligands (IGF-1 and IGF-2), two IGF receptors (IGFR1 and IGFR2), and multiple IGF-binding proteins (IGFBPs). The IGFs, named so due to their structural similarity with insulin, are active peptides imperative for producing the physiological effects of growth hormone. The binding of IGF to IGF1R on the cell surface of target tissues can regulate apoptosis, proliferation, aging, and other physiological processes closely related to the growth and development of the body. While IGFs can be synthesized and secreted by multiple body tissues, the liver is the primary source of circulating IGFs. During embryonic development, IGFs play a critical role, which exceeds that of growth hormones. Detection of IGF-2 and its receptor at the two-cell stage indicates its essential role during this stage.
FIgure 1. Diagram showing crosstalk between the hypothalamic pituitary GH and IGF-1 axis and endocrine organ. (Bleach R, et al., 2021)
IGF-1 has various biological effects, such as promoting bone formation, protein synthesis, muscle glucose uptake, nerve survival, and myelin synthesis. Growth hormone (GH) regulates IGF-1 levels, which mediate several of GH's effects. IGF-1 deficiency inhibits bone growth and overall growth and development, resulting in shorter-than-normal height in children. Embryonic development is mildly delayed by mutations in either the growth hormone or growth hormone receptor genes. However, mice with mutations in the IGF-1 gene experience severe embryonic developmental delays. Additionally, IGF-1 plays a crucial role in regulating osteoblast function and metabolism, decreasing collagen degeneration, increasing bone deposition, and promoting osteoblast differentiation, maturation, and replenishment. Studies have shown that individuals with osteoporosis exhibit markedly reduced serum levels of IGF-I compared to healthy individuals. At present, IGF-I is also recognized for its efficacy in ameliorating insulin resistance, and administering high doses of IGF-I can serve to regulate metabolic disorders while concurrently reinstating insulin sensitivity.
IGF-2 plays an important role in regulating blood sugar, metabolism, and growth, as well as promoting healthy brain development and function. By binding to the appropriate receptors, IGF-2 activates signaling that regulates neuronal growth and activity, and disruption of this signaling pathway has been implicated in cognitive decline and diseases such as Alzheimer's disease (AD). Studies have confirmed that the inhibition of IGF-2 hinders the formation of memories involved in learning. Both short-term and long-term memory are compromised in the absence of IGF-2.
IGFBP3 is highly prevalent in the blood after birth and has anti-proliferative, anti-mitotic, and pro-apoptotic effects. It binds to IGFs and impedes their degradation while facilitating their conveyance throughout the body. Additionally, IGFBP3 modifies the structure of IGFs, altering their specific receptor interactions. Due to its dependence on GH and correlation with the amount of GH secreted, the measurement of serum IGFBP3 assists in identifying abnormal GH secretion and serves as a valuable indicator for detecting GH deficiency.
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