Effect of chronic renal failure and growth hormone therapy on the insulin-like growth factors and their binding proteins.
Children with chronic-renal failure (CRF) are often growth retarded, and abnormalities of the growth hormone (GH)/insulin-like growth factor (IGF) axis in CRF may contribute to this poor growth. Despite normal IGF levels in CRF serum, IGF bioactivity is low due to excess IGF-binding proteins (IGFBPs) in the 35-kDa serum fractions. Levels of IGFBP-1, -2, -4 and -6, and a 29-kDa IGFBP-3 fragment, are high in CRF serum, and levels of intact IGFBP- 1 and -2 correlate negatively with height. IGFBP-1 levels may be high due to insulin resistance, suggesting that the FKHR family of transcription factors may play a role in the overexpression of IGFBP-1, and other growth inhibitors, in CRF. GH-treated CRF children show catch-up growth that correlates positively with a rise in each component of the 150-kDa serum ternary complex (IGF-I or -II/IGFBP-3 or -5/acid-labile subunit); IGFBP-1, -2 and -6 levels do not rise, but serum IGF bioactivity does. Thus, GH increases levels of IGFs and ternary complexes in CRF serum. It is likely that increased IGFs contribute to catch-up growth by overcoming the inhibitory effects of excess IGFBPs present in the CRF milieu.
Powell
D R
DR
Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Liu
F
F
Baker
B K
BK
Hinzt
R L
RL
Kale
A
A
Suwanichkul
A
A
Durham
S K
SK
D000818:Animals; D002675:Child, Preschool; D006131:Growth Inhibitors / Q000502:physiology; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism* / Q000502:physiology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013002:Somatomedins / Q000378:metabolism*; D017211:Treatment Failure
D006131:Growth Inhibitors; D018969:Insulin-Like Growth Factor Binding Proteins; D011994:Recombinant Proteins; D013002:Somatomedins; D019382:Human Growth Hormone