Evidence suggesting that insulin-like growth factor-I is necessary for the trophic effects of insulin on cartilage growth in vivo.

The possibility that insulin-stimulated cartilage growth in hypophysectomized rats involves local production of insulin-like growth factor I (IGF-I) was investigated. Osmotic minipumps with attached catheters were used to infuse insulin into the right hindlimb of rats via the common iliac artery for 7 days starting 14 days after pituitary removal. The left, noninfused limb served as an internal control. Doses of insulin ranging from 0.25 to 50 mU/day caused significant increases in the tibial epiphyseal plate width (TEPW) of the infused limbs. The optimal dose of 1.25 mU/day increased the TEPW by 51 microns. Immunohistochemical analysis with an antiserum to human IGF-I showed that the growth response to the optimal dose was accompanied by the accumulation of IGF-I in the chondrocytes in the tibial plate. Infusion of insulin at a dose of 10 mU/day increased the TEPW by 18.6 +/- 3.0 microns. When the same dose of insulin was infused with the antiserum to human IGF-I, the growth response was completely nullified. These results indicate that cartilage cells in hypophysectomized rats are highly sensitive to the direct growth-promoting action of insulin. Furthermore, the growth effect appears to be mediated by or dependent on local production of IGF-I.