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.

Anthropometric factors and risk of melanoma in women: A pooled analysis

“…54 Another possibility is an endocrine etiology, since height is correlated with serum hormones that may play a role in carcinogenesis. 55,56 It also may be possible that a behavioral correlate of body height is related to sun exposure, such as participation in outdoor sporting activities, 57 that increases the likelihood of developing melanoma. However, our adjustment for sun exposure-related factors generally had little to no effect on our results.…”

“…55,56,58 Accumulating evidence suggests that adult weight gain may be a more relevant variable to assess the effect of weight on health than body weight or BMI. 59 We cannot explain why the association with weight gain was stronger for melanomas on the lower limbs.…”

The effect of economic status on height, insulin-like growth factor (IGF)-I and IGF binding protein-3 concentrations in healthy Turkish children

“…Serum levels of IGF-I and IGFBP-3 exhibit little diurnal variation (Jorgensen et al, 1990) and reflect endogenous GH secretion in healthy children (Blum et al, 1993). In addition to GH status, chronological age, gonadal maturation and nutrition also have influence on IGF-I concentration significantly (Bouhaddioui et al, 1989;Lopez-Jaramillo et al, 1992;Juul et al, 1994Juul et al, , 1995. It has been demonstrated that plasma IGF-I levels are lower in malnourished children (Unterman et al, 1985;Bouhaddioui et al, 1989;Wan Nazaimoon et al, 1996;Beaune et al, 1997).…”

Insulin-like growth factor-I and prostate cancer: a meta-analysis

“…Since IGFs are regulated by both endocrine and paracrine mechanisms, the action of IGFs in tissue, however, is determined not only by the circulating levels of IGFs and IGF-binding proteins (IGFBPs), but also by local production (Jones and Clemmons, 1995). There is a large interpersonal variability in the circulating concentrations of IGF-I and IGFBP-3 (a major IGFBP in the circulation) (Juul et al, 1994(Juul et al, , 1995.…”