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

H. Kanety, A. Karasik, B. Klinger, A. Silbergeld, Z. Laron

Research output: Contribution to journalArticlepeer-review

Abstract

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 reveald an extremely low IGFBP-3 level. A striking progressive increased 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.

Original languageEnglish
Pages (from-to)144-149
Number of pages6
JournalActa Endocrinologica
Volume128
Issue number2
DOIs
StatePublished - 1993
Externally publishedYes

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