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.
Alarid
E T
ET
Department of Integrative Biology, University of California, Berkeley 94720.
Schlechter
N L
NL
Russell
S M
SM
Nicoll
C S
CS
D000818:Animals; D002356:Cartilage / Q000187:drug effects* / Q000254:growth & development; D013006:Growth Hormone / Q000494:pharmacology; D007016:Hypophysectomy; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000502:physiology*; D008297:Male; D051381:Rats
D007328:Insulin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone