Serum concentrations of free and total insulin-like growth factor-I, IGF binding proteins -1 and -3 and IGFBP-3 protease activity in boys with normal or precocious puberty

Clin Endocrinol (Oxf). 1996 May;44(5):515-23. doi: 10.1046/j.1365-2265.1996.711531.x.


Objective: Circulating IGF-I and IGF binding protein-3 (IGFBP-3) levels both increase in puberty where growth velocity is high. The amount of free IGF-I is dependent on the IGF-I level and on the concentrations of the specific IGFBPs. Furthermore, IGFBP-3 proteolysis regulates the bioavailability of IGF-I. However, the concentration of free IGF-I and possible IGFBP-3 proteolytic activity in puberty has not previously been studied.

Subjects and measurements: We investigated serum levels of easily dissociable IGF-I concentrations and ultrafiltrated free IGF-I levels by specific assays in 60 healthy boys and in 5 boys with precocious puberty before and during GnRH agonist treatment. In addition, total serum IGF-I, IGFBP-1 and IGFBP-3 levels as well as IGFBP-3 protease activity were determined.

Results: Free (dissociable and ultrafiltrated) IGF-I concentrations were significantly higher in pubertal boys than in prepubertal children and correlated significantly with the molar ratio between IGF-I and IGFBP-3 (r = 0.69, P < 0.0001 and r = 0.54, P = 0.0008, respectively) and inversely with IGFBP-1 (r = -0.47, P < 0.0001 and r = -0.43, P = 0.0003, respectively). Multiple regression analysis suggested that IGFBP-3 level, and not IGFBP-1, was the major determinant of the free IGF-I serum level in normal boys. Free IGF-I levels were elevated in boys with precocious puberty and decreased during GnRH treatment. IGFBP-3 proteolysis was constant throughout puberty (mean 20%).

Conclusions: We conclude that easily dissociable and ultrafiltrated free IGF-I serum levels are increased in boys with normal and precocious puberty and suggest that the increased free IGF-I serum concentration in puberty primarily reflects changes in total concentrations of IGF-I and IGFBPs secondary to increased GH secretion, but that it is not influenced by changes in IGFBP-3 proteolysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Analysis of Variance
  • Androgen Antagonists / therapeutic use
  • Buserelin / therapeutic use
  • Child
  • Cyproterone Acetate / therapeutic use
  • Endopeptidases / blood*
  • Gonadotropin-Releasing Hormone / agonists
  • Gonadotropin-Releasing Hormone / therapeutic use
  • Humans
  • Insulin-Like Growth Factor Binding Proteins / blood*
  • Insulin-Like Growth Factor I / metabolism*
  • Male
  • Puberty / blood*
  • Puberty, Precocious / blood*
  • Puberty, Precocious / drug therapy
  • Regression Analysis


  • Androgen Antagonists
  • Insulin-Like Growth Factor Binding Proteins
  • Gonadotropin-Releasing Hormone
  • Cyproterone Acetate
  • Insulin-Like Growth Factor I
  • Endopeptidases
  • insulin-like growth factor binding protein-3 protease
  • Buserelin