Juul A, Flyvbjerg A, Frystyk J, Müller J, Skakkebaek N E
Department of Growth and Reproduction, National University Hospital, Copenhagen, Denmark.
Clin Endocrinol (Oxf). 1996 May;44(5):515-23. doi: 10.1046/j.1365-2265.1996.711531.x.
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.
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.
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%).
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.
在生长速度较快的青春期，循环中的胰岛素样生长因子-I（IGF-I）和胰岛素样生长因子结合蛋白-3（IGFBP-3）水平均会升高。游离IGF-I的量取决于IGF-I水平以及特定IGFBP的浓度。此外，IGFBP-3蛋白水解作用调节IGF-I的生物利用度。然而，青春期游离IGF-I的浓度以及可能存在的IGFBP-3蛋白水解活性此前尚未得到研究。
我们通过特定检测方法，对60名健康男孩以及5名性早熟男孩在GnRH激动剂治疗前后血清中易解离的IGF-I浓度和超滤后的游离IGF-I水平进行了研究。此外，还测定了血清总IGF-I、IGFBP-1和IGFBP-3水平以及IGFBP-3蛋白酶活性。
青春期男孩的游离（易解离和超滤后）IGF-I浓度显著高于青春期前儿童，且与IGF-I和IGFBP-3之间的摩尔比显著相关（分别为r = 0.69，P < 0.0001和r = 0.54，P = 0.0008），与IGFBP-1呈负相关（分别为r = -0.47，P < 0.0001和r = -0.43，P = 0.0003）。多元回归分析表明，在正常男孩中，IGFBP-3水平而非IGFBP-1水平是游离IGF-I血清水平的主要决定因素。性早熟男孩的游离IGF-I水平升高，而在GnRH治疗期间降低。IGFBP-3蛋白水解作用在整个青春期保持恒定（平均为20%）。
我们得出结论，正常和性早熟男孩血清中易解离和超滤后的游离IGF-I水平均升高，提示青春期游离IGF-I血清浓度升高主要反映了生长激素分泌增加导致的IGF-I和IGFBPs总浓度变化，但不受IGFBP-3蛋白水解作用变化的影响。
