Long-term treatment of Laron type dwarfs with insulin-like growth factor-1 increases serum insulin-like growth factor-binding protein-3 in the absence of growth hormone activity.
Insulin-like growth factor binding protein-3 (IGFBP-3) is the major carrier of insulin-like growth factor I (IGF-I) in serum, and its production is growth hormone (GH) dependent. It is unclear whether in humans IGFBP-3 production is directly regulated by GH or mediated via IGF-I. We addressed this question in six patients with Laron-type dwarfism, a syndrome characterized by the absence of GH receptor activity (LTD), who were chronically treated with recombinant IGF-I. Analysis of the electrophoretic profiles of serum IGFBPs in these patients by Western ligand blotting revealed an extremely low IGFBP-3 level. A striking progressive increase in serum IGFBP-3 was observed with continuous treatment, despite the absence of GH action. In LTD children, serum IGFBP-3 increased up to 19-fold after six months of therapy and equalled levels observed in controls, whereas in adult LTD patients the increase was smaller. A rise in serum levels of 34, 30 and 24 kDa BPs (presumably IGFBP-2, -1 and -4, respectively was also noted with chronic IGF-I therapy. This proof of GH-independent induction of IGFBP-3 by IGF-I may be a major advantage in the therapeutic use of biosynthetic IGF-I in several types of short stature children.
Kanety
H
H
Institute of Endocrinology, Chaim Sheba Medical Center, Tel Hashomer, Israel.
Karasik
A
A
Klinger
B
B
Silbergeld
A
A
Laron
Z
Z
D000293:Adolescent; D000328:Adult; D001345:Autoradiography; D015153:Blotting, Western; D002352:Carrier Proteins / Q000097:blood / Q000187:drug effects*; D002675:Child, Preschool; D004392:Dwarfism / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D013006:Growth Hormone / Q000502:physiology*; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000172:deficiency / Q000627:therapeutic use*; D008297:Male; D011994:Recombinant Proteins / Q000627:therapeutic use
D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone