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.
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.


METHODS
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.
Juul
A
A
Department of Growth and Reproduction, National University Hospital, Copenhagen, Denmark.
Flyvbjerg
A
A
Frystyk
J
J
Müller
J
J
Skakkebaek
N E
NE
D000293:Adolescent; D000704:Analysis of Variance; D000726:Androgen Antagonists / Q000627:therapeutic use; D002064:Buserelin / Q000627:therapeutic use; D002648:Child; D017373:Cyproterone Acetate / Q000627:therapeutic use; D010450:Endopeptidases / Q000097:blood*; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists / Q000627:therapeutic use; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D011627:Puberty / Q000097:blood*; D011629:Puberty, Precocious / Q000097:blood* / Q000188:drug therapy; D012044:Regression Analysis
D000726:Androgen Antagonists; D018969:Insulin-Like Growth Factor Binding Proteins; D007987:Gonadotropin-Releasing Hormone; D017373:Cyproterone Acetate; D007334:Insulin-Like Growth Factor I; D010450:Endopeptidases; C080473:insulin-like growth factor binding protein-3 protease; D002064:Buserelin