Serum levels of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) in healthy infants, children, and adolescents: the relation to IGF-I, IGF-II, IGFBP-1, IGFBP-2, age, sex, body mass index, and pubertal maturation

A Juul; P Dalgaard; W F Blum; P Bang; Katrine Pinholt Hall; K F Michaelsen; J Müller; N E Skakkebaek

Serum levels of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) in healthy infants, children, and adolescents: the relation to IGF-I, IGF-II, IGFBP-1, IGFBP-2, age, sex, body mass index, and pubertal maturation

A Juul, P Dalgaard, W F Blum, P Bang, Katrine Pinholt Hall, K F Michaelsen, J Müller, N E Skakkebaek

400 Citations (Scopus)

Abstract

Circulating IGF-I and -II are bound to specific insulin-like growth factor (IGF)-binding proteins (IGFBPs), of which IGFBP-3 binds the majority of the IGFs. IGFBP-3 levels are regulated by GH and have been suggested to provide additional information on GH secretory capacity compared to IGF-I. However, the diagnostic value of IGFBP-3 is still controversial, perhaps because the quality of the available normative data for IGFBP-3 varies. It has recently been shown that a large number of individuals is required to establish reference ranges for IGF-I that take into account age, sex, body mass index (BMI), and pubertal stage. Therefore, we measured IGFBP-3, IGF-I, IGF-II, IGFBP-1, and IGFBP-2 levels by RIA in 907 healthy children to establish well characterized normative data on IGFBP-3 according to age, sex, and pubertal stage and to study the complex relationship between IGFs and their BPs in puberty. We found that IGFBP-3 levels increase with age in children, with maximal levels in puberty; girls experience peak values approximately 1 yr earlier than boys. Age, sex, height, BMI, and pubertal maturation were all important factors in determining the circulating levels of IGFBP-3, whereas IGF-I levels were unaffected by BMI. Comparison of IGFBP-3 with IGF-1 concentrations revealed that they did not exhibit the same developmental pattern in puberty. IGF-I levels increased to relatively higher levels than IGFBP-3, leading to an increasing molar ratio between IGF-I and IGFBP-3 in puberty, when growth velocity is high. Concomitantly, IGF-II and IGFBP-2 levels were unchanged throughout puberty, whereas IGFBP-1 levels declined with age in prepubertal children, with lowest values in puberty. There was a highly significant correlation between IGF-I and -II and IGFBP-3 on a molar basis (r = 0.84; P <0.0001). Thus, we speculate that IGFBP-3 is pivotal for circulating IGF bioactivity and that the increase in the molar ratio between IGF-I and IGFBP-3 reflects an increase in free, biologically active IGF-I. In conclusion, we have provided normative data on a large group of healthy individuals and conclude that age, sex, height, BMI, and pubertal maturation have to be taken into account before a single IGFBP-3 value in a growth-retarded child can be evaluated properly.

Original language	English
Journal	Journal of Clinical Endocrinology and Metabolism
Volume	80
Issue number	8
Pages (from-to)	2534-42
Number of pages	9
ISSN	0021-972X
Publication status	Published - 1995

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Juul, A., Dalgaard, P., Blum, W. F., Bang, P., Hall, K. P., Michaelsen, K. F., Müller, J., & Skakkebaek, N. E. (1995). Serum levels of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) in healthy infants, children, and adolescents: the relation to IGF-I, IGF-II, IGFBP-1, IGFBP-2, age, sex, body mass index, and pubertal maturation. Journal of Clinical Endocrinology and Metabolism, 80(8), 2534-42.

Serum levels of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) in healthy infants, children, and adolescents : the relation to IGF-I, IGF-II, IGFBP-1, IGFBP-2, age, sex, body mass index, and pubertal maturation. / Juul, A; Dalgaard, P; Blum, W F et al.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 80, No. 8, 1995, p. 2534-42.

Research output: Contribution to journal › Journal article › Research › peer-review

Juul, A, Dalgaard, P, Blum, WF, Bang, P, Hall, KP, Michaelsen, KF, Müller, J & Skakkebaek, NE 1995, 'Serum levels of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) in healthy infants, children, and adolescents: the relation to IGF-I, IGF-II, IGFBP-1, IGFBP-2, age, sex, body mass index, and pubertal maturation', Journal of Clinical Endocrinology and Metabolism, vol. 80, no. 8, pp. 2534-42.

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title = "Serum levels of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) in healthy infants, children, and adolescents: the relation to IGF-I, IGF-II, IGFBP-1, IGFBP-2, age, sex, body mass index, and pubertal maturation",

abstract = "Circulating IGF-I and -II are bound to specific insulin-like growth factor (IGF)-binding proteins (IGFBPs), of which IGFBP-3 binds the majority of the IGFs. IGFBP-3 levels are regulated by GH and have been suggested to provide additional information on GH secretory capacity compared to IGF-I. However, the diagnostic value of IGFBP-3 is still controversial, perhaps because the quality of the available normative data for IGFBP-3 varies. It has recently been shown that a large number of individuals is required to establish reference ranges for IGF-I that take into account age, sex, body mass index (BMI), and pubertal stage. Therefore, we measured IGFBP-3, IGF-I, IGF-II, IGFBP-1, and IGFBP-2 levels by RIA in 907 healthy children to establish well characterized normative data on IGFBP-3 according to age, sex, and pubertal stage and to study the complex relationship between IGFs and their BPs in puberty. We found that IGFBP-3 levels increase with age in children, with maximal levels in puberty; girls experience peak values approximately 1 yr earlier than boys. Age, sex, height, BMI, and pubertal maturation were all important factors in determining the circulating levels of IGFBP-3, whereas IGF-I levels were unaffected by BMI. Comparison of IGFBP-3 with IGF-1 concentrations revealed that they did not exhibit the same developmental pattern in puberty. IGF-I levels increased to relatively higher levels than IGFBP-3, leading to an increasing molar ratio between IGF-I and IGFBP-3 in puberty, when growth velocity is high. Concomitantly, IGF-II and IGFBP-2 levels were unchanged throughout puberty, whereas IGFBP-1 levels declined with age in prepubertal children, with lowest values in puberty. There was a highly significant correlation between IGF-I and -II and IGFBP-3 on a molar basis (r = 0.84; P <0.0001). Thus, we speculate that IGFBP-3 is pivotal for circulating IGF bioactivity and that the increase in the molar ratio between IGF-I and IGFBP-3 reflects an increase in free, biologically active IGF-I. In conclusion, we have provided normative data on a large group of healthy individuals and conclude that age, sex, height, BMI, and pubertal maturation have to be taken into account before a single IGFBP-3 value in a growth-retarded child can be evaluated properly.",

author = "A Juul and P Dalgaard and Blum, {W F} and P Bang and Hall, {Katrine Pinholt} and Michaelsen, {K F} and J M{\"u}ller and Skakkebaek, {N E}",

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language = "English",

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pages = "2534--42",

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TY - JOUR

T1 - Serum levels of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) in healthy infants, children, and adolescents

T2 - the relation to IGF-I, IGF-II, IGFBP-1, IGFBP-2, age, sex, body mass index, and pubertal maturation

AU - Juul, A

AU - Dalgaard, P

AU - Blum, W F

AU - Bang, P

AU - Hall, Katrine Pinholt

AU - Michaelsen, K F

AU - Müller, J

AU - Skakkebaek, N E

PY - 1995

Y1 - 1995

N2 - Circulating IGF-I and -II are bound to specific insulin-like growth factor (IGF)-binding proteins (IGFBPs), of which IGFBP-3 binds the majority of the IGFs. IGFBP-3 levels are regulated by GH and have been suggested to provide additional information on GH secretory capacity compared to IGF-I. However, the diagnostic value of IGFBP-3 is still controversial, perhaps because the quality of the available normative data for IGFBP-3 varies. It has recently been shown that a large number of individuals is required to establish reference ranges for IGF-I that take into account age, sex, body mass index (BMI), and pubertal stage. Therefore, we measured IGFBP-3, IGF-I, IGF-II, IGFBP-1, and IGFBP-2 levels by RIA in 907 healthy children to establish well characterized normative data on IGFBP-3 according to age, sex, and pubertal stage and to study the complex relationship between IGFs and their BPs in puberty. We found that IGFBP-3 levels increase with age in children, with maximal levels in puberty; girls experience peak values approximately 1 yr earlier than boys. Age, sex, height, BMI, and pubertal maturation were all important factors in determining the circulating levels of IGFBP-3, whereas IGF-I levels were unaffected by BMI. Comparison of IGFBP-3 with IGF-1 concentrations revealed that they did not exhibit the same developmental pattern in puberty. IGF-I levels increased to relatively higher levels than IGFBP-3, leading to an increasing molar ratio between IGF-I and IGFBP-3 in puberty, when growth velocity is high. Concomitantly, IGF-II and IGFBP-2 levels were unchanged throughout puberty, whereas IGFBP-1 levels declined with age in prepubertal children, with lowest values in puberty. There was a highly significant correlation between IGF-I and -II and IGFBP-3 on a molar basis (r = 0.84; P <0.0001). Thus, we speculate that IGFBP-3 is pivotal for circulating IGF bioactivity and that the increase in the molar ratio between IGF-I and IGFBP-3 reflects an increase in free, biologically active IGF-I. In conclusion, we have provided normative data on a large group of healthy individuals and conclude that age, sex, height, BMI, and pubertal maturation have to be taken into account before a single IGFBP-3 value in a growth-retarded child can be evaluated properly.

AB - Circulating IGF-I and -II are bound to specific insulin-like growth factor (IGF)-binding proteins (IGFBPs), of which IGFBP-3 binds the majority of the IGFs. IGFBP-3 levels are regulated by GH and have been suggested to provide additional information on GH secretory capacity compared to IGF-I. However, the diagnostic value of IGFBP-3 is still controversial, perhaps because the quality of the available normative data for IGFBP-3 varies. It has recently been shown that a large number of individuals is required to establish reference ranges for IGF-I that take into account age, sex, body mass index (BMI), and pubertal stage. Therefore, we measured IGFBP-3, IGF-I, IGF-II, IGFBP-1, and IGFBP-2 levels by RIA in 907 healthy children to establish well characterized normative data on IGFBP-3 according to age, sex, and pubertal stage and to study the complex relationship between IGFs and their BPs in puberty. We found that IGFBP-3 levels increase with age in children, with maximal levels in puberty; girls experience peak values approximately 1 yr earlier than boys. Age, sex, height, BMI, and pubertal maturation were all important factors in determining the circulating levels of IGFBP-3, whereas IGF-I levels were unaffected by BMI. Comparison of IGFBP-3 with IGF-1 concentrations revealed that they did not exhibit the same developmental pattern in puberty. IGF-I levels increased to relatively higher levels than IGFBP-3, leading to an increasing molar ratio between IGF-I and IGFBP-3 in puberty, when growth velocity is high. Concomitantly, IGF-II and IGFBP-2 levels were unchanged throughout puberty, whereas IGFBP-1 levels declined with age in prepubertal children, with lowest values in puberty. There was a highly significant correlation between IGF-I and -II and IGFBP-3 on a molar basis (r = 0.84; P <0.0001). Thus, we speculate that IGFBP-3 is pivotal for circulating IGF bioactivity and that the increase in the molar ratio between IGF-I and IGFBP-3 reflects an increase in free, biologically active IGF-I. In conclusion, we have provided normative data on a large group of healthy individuals and conclude that age, sex, height, BMI, and pubertal maturation have to be taken into account before a single IGFBP-3 value in a growth-retarded child can be evaluated properly.

M3 - Journal article

SN - 0021-972X

VL - 80

SP - 2534

EP - 2542

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 8

ER -