Insulin‐like growth factor binding protein 2 (IGFBP‐2) separates hypertrophic and hyperplastic effects of growth hormone (GH)/IGF‐I excess on adrenocortical cells in vivo

Abstract Although insulin-like growth factor-binding protein-2 (IGFBP-2) is an abundant IGFBP in fetal and postnatal plasma, its regulation is not yet clearly understood. To address this question in sheep, we purified ovine IGFBP-2 and developed a homologous radioimmunoassay. We have studied its ontogenesis and measured serum concentrations of ovine IGFBP-2 after bovine growth hormone (bGH), ovine placental lactogen (oPL) and IGF-I treatment. Concentrations of IGFBP-2 were high at 125 days of gestation (550 ± 15 μg/l) but fell after birth P<0·05) and plateaued after 1 year of age (340 ± 20 μg/l). In lactating ewes, bGH treatment for 7 days significantly reduced (21%; P<0·05) IGFBP-2 relative to the saline-treated group. Similarly, in neonatal lambs, bGH treatment from day 3 to day 23 of life reduced (P<0·05) IGFBP-2 by 23% relative to the saline-treated group. oPL had no effect on serum levels of IGFBP-2 in the ewe or the neonatal lamb. In well-fed yearling lambs, treatment with IGF-I reduced IGFBP-2 values by 27% (P<0·05) relative to control animals. In yearling lambs, reduced nutrition increased plasma IGFBP-2 (41%; P<0·05). However this increase was abolished by IGF-I treatment. The changes in plasma levels of IGFBP-2 were positively related to changes in IGF-II while there was a negative relationship between circulating IGF-I and IGFBP-2 such that both IGF-I and IGF-II may play a role in the regulation of IGFBP-2 in serum. Journal of Endocrinology (1995) 144, 75–82

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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

Acta Endocrinologica ◽

10.1530/acta.0.1280144 ◽

1993 ◽

Vol 128 (2) ◽

pp. 144-149 ◽

Cited By ~ 41

Author(s):

Hannah Kanety ◽

Avraham Karasik ◽

Beatrice Klinger ◽

Aviva Silbergeld ◽

Zvi Laron

Keyword(s):

Growth Hormone ◽

Growth Factor ◽

Binding Protein ◽

Serum Insulin ◽

Continuous Treatment ◽

Insulin Like Growth Factor ◽

Factor Binding ◽

Long Term Treatment ◽

Igf I ◽

Igfbp 3

Insulin-like growth factor binding protein-3 (IGFBP-3) is the major carrier of insulin-like growth factor I (IGF-1) 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-1 may be a major advantage in the therapeutic use of biosynthetic IGF-I in several types of short stature children.

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