Growth hormone insensitivity syndromes: a preliminary report on changes in insulin-like growth factors and their binding proteins during treatment with recombinant insulin-like growth factor I. Kabi Pharmacia Study Group on Insulin-like Growth Factor I Treatment in Growth Hormone Insensitivity Syndromes.
Serum levels of insulin-like growth factor (IGF) binding proteins (IGFBPs) 1, 2 and 3 were studied by radioimmunoassay in 29 patients with growth hormone (GH) insensitivity syndromes (GHIS) before and during treatment with IGF-I. As in normal subjects, there was a highly significant correlation between IGFs and IGFBP-3 but not between IGFs and the other binding proteins, though IGFBP-3 represented only about one-third of the total IGFBP concentration. In 6 patients with GH deficiency and in 5 patients with GHIS, the pharmacokinetic profile of IGF-I after a single injection was strongly dependent on the IGFBP-3 concentration. A slight but significant increase in IGFBP-3 was observed coincident with the IGF-I peak, whereas IGFBP-2 increased after a delay of about 10 hours. In the patients with GHIS, chronic IGF-I treatment, with twice-daily injections for 6 months, caused a significant steady decline of IGF-II and an increase in IGFBP-2, but had no effect on IGFBP-1 and IGFBP-3 levels. During IGF-I treatment, an inverse relationship between baseline IGF-I and GH levels was observed. The data suggest that total IGF-I and IGF-II serum levels are determined mainly by IGFBP-3, even in extreme situations such as GHIS, while other IGFBPs are less important. The IGFBP-3 concentration seems to be a major regulator of the pharmacokinetics of exogenous IGF-I, which, in turn, influences IGFBP-3 levels. This effect of IGF-I on IGFBP-3 is not through induction of IGFBP-3 synthesis, but possibly by reduction of IGFBP-3 clearance.(ABSTRACT TRUNCATED AT 250 WORDS)
Blum
W F
WF
University Children's Hospital, Tübingen, Germany.
Hall
K
K
Ranke
M B
MB
Wilton
P
P
D000293:Adolescent; D000328:Adult; D002352:Carrier Proteins / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D004392:Dwarfism / Q000097:blood / Q000188:drug therapy*; D005260:Female; D013006:Growth Hormone / Q000172:deficiency; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007335:Insulin-Like Growth Factor II / Q000493:pharmacokinetics; D008297:Male; D008954:Models, Biological; D011986:Receptors, Somatotropin / Q000172:deficiency*; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000627:therapeutic use; D013002:Somatomedins / Q000378:metabolism*
D002352:Carrier Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018969:Insulin-Like Growth Factor Binding Proteins; D011986:Receptors, Somatotropin; D011994:Recombinant Proteins; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D013006:Growth Hormone