Insulin-like growth factor 1 axis (IGF-1 axis)

The insulin-like growth factor 1 axis refers to an evolutionarily conserved endocrine and paracrine system comprising insulin-like growth factor 1 (IGF-1), its receptor (IGF-1R), other ligands (IGF-2), multiple high-affinity binding proteins (IGFBP1–7), and IGFBP proteases[1][3][4][6]. This axis is central to the regulation of cell growth, proliferation, survival, and metabolism and is tightly regulated by growth hormone (GH), primarily from the anterior pituitary. IGF-1 is chiefly produced in the liver in response to GH, but also synthesized in many tissues for local effects[2][4][5][6]. The axis mediates its effects via receptor tyrosine kinase signaling pathways, notably the PI3K-Akt and MAPK pathways, promoting anabolic processes, cell survival, and tissue growth, while inhibiting apoptosis[5]. Dysregulation of IGF-1 axis signaling is implicated in the development of several diseases—notably cancer (as a driver of proliferation and survival), diabetes (through effects on glucose homeostasis), cardiovascular disease, and growth disorders[3][6]. Clinically, therapeutic modulation of the axis includes recombinant growth hormone, synthetic IGF-1 (mecasermin) for growth failure, and investigational agents targeting IGF-1R in oncology[2][3]. Monitoring of serum IGF-1 and IGFBP-3 serves as a useful biomarker for growth-related conditions and therapy response, but manipulation or dysregulation of the axis poses significant safety risks including potential for malignancy and metabolic complications[2][4][6].

Other names

Growth hormone/IGF-1 axisIGF axisGH–IGF-I axis

Agonism at IGF-1 receptor (promoting or mimicking IGF-1 activity) Antagonism or inhibition of IGF-1 receptor (blocking activity to reduce proliferation in cancer)