TY - JOUR

T1 - Why Do Normal Children Have Acromegalic Levels of IGF-I During Puberty?

AU - Juul, Anders

AU - Skakkebæk, Niels E

N1 - Copyright © 2019 Endocrine Society.

PY - 2019

Y1 - 2019

N2 - CONTEXT: The rapid pubertal height growth is unique to humans, but why do we have it? Although the spurt contributes 13% to 15% to the final adult height, we hypothesized that the biological significance of the high acromegalic levels of GH and IGF-I, which are behind the pubertal growth spurt, might primarily occur to stimulate the reproductive organs.EVIDENCE SYNTHESIS: Animal data have demonstrated that adult Igf1 and Igf2 gene knockout mice that survive show a dramatic reduction in the size of the reproductive organs and are infertile. In humans, case reports of mutations in the genes affecting the GH-IGF axis and growth (GH, GHRH, GH-R, STAT5b, IGF-I, IGF-II, IGF-1R, PAPPA2) are also characterized by delayed pubertal onset and micropenis. Furthermore, GH treatment will tend to normalize the penile size in patients with GH deficiency. Thus, the endocrine effects of high IGF-I levels might be needed for the transition of the sexual organs, including the secondary sex characteristics, from the "dormant" stages of childhood into fully functioning reproductive systems. The peak IGF-I levels, on average, occur 2 years after the peak height growth velocity, suggesting reasons other than longitudinal growth for the high IGF-I levels, and remain high in the years after the height spurt, when the reproductive systems become fully functional.CONCLUSION: We suggest that the serum levels of IGF-I should be monitored in children with poor development of sexual organs, although it remains to be investigated whether GH should be added to sex steroids in the management of hypogonadism for some pubertal children (e.g., boys with micropenis).

AB - CONTEXT: The rapid pubertal height growth is unique to humans, but why do we have it? Although the spurt contributes 13% to 15% to the final adult height, we hypothesized that the biological significance of the high acromegalic levels of GH and IGF-I, which are behind the pubertal growth spurt, might primarily occur to stimulate the reproductive organs.EVIDENCE SYNTHESIS: Animal data have demonstrated that adult Igf1 and Igf2 gene knockout mice that survive show a dramatic reduction in the size of the reproductive organs and are infertile. In humans, case reports of mutations in the genes affecting the GH-IGF axis and growth (GH, GHRH, GH-R, STAT5b, IGF-I, IGF-II, IGF-1R, PAPPA2) are also characterized by delayed pubertal onset and micropenis. Furthermore, GH treatment will tend to normalize the penile size in patients with GH deficiency. Thus, the endocrine effects of high IGF-I levels might be needed for the transition of the sexual organs, including the secondary sex characteristics, from the "dormant" stages of childhood into fully functioning reproductive systems. The peak IGF-I levels, on average, occur 2 years after the peak height growth velocity, suggesting reasons other than longitudinal growth for the high IGF-I levels, and remain high in the years after the height spurt, when the reproductive systems become fully functional.CONCLUSION: We suggest that the serum levels of IGF-I should be monitored in children with poor development of sexual organs, although it remains to be investigated whether GH should be added to sex steroids in the management of hypogonadism for some pubertal children (e.g., boys with micropenis).

U2 - 10.1210/jc.2018-02099

DO - 10.1210/jc.2018-02099

M3 - Journal article

C2 - 30840065

VL - 104

SP - 2770

EP - 2776

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 7

ER -