Growth variations with opposite clinical outcomes and the emerging role of IGF-1

Normal growth pattern variations [i.e., constitutional advancement and constitutional delay of growth and puberty (CAGP and CDGP)] are the mirror image of each other and are associated with early puberty (EP) and delayed puberty (DP), respectively. Differences between CAGP and CDGP relate not only to auxological characteristics (height, weight) but also to insulin-like growth factor-1 (IGF-1). IGF-1 levels in CAGP are above average whereas in CDGP they are below average, suggesting a role for IGF-1 in the induction of these growth patterns. Herein, we provide data suggesting that early activation of the growth hormone (GH)/IGF-1 axis induces the growth pattern of CAGP. Moreover, we suggest that IGF-1 is a decisive factor for the release of the gonadotropin-releasing hormone (GnRH) inhibition brake that occurs in prepuberty. It is therefore crucial for puberty onset. Constitutional advancement of growth and puberty (CAGP) is the mirror image of constitutional delay of growth and puberty (CDGP). CAGP is associated with idiopathic precocious puberty and early puberty in girls.Girls destined for early puberty development, at the age of 8 years when still prepubertal, have increased IGF-1 levels, suggesting a role for IGF-1 in early growth acceleration and early pubertal onset.IGF-1 has emerged as a major determinant of the onset of puberty. IGF-1 suppresses dynorphin; thus, it releases the hypothalamic brake on prepubertal GnRH secretion.We propose that the steep increase of IGF-1 levels that occurs in girls who are biologically mature enough to enter puberty, releases the GnRH inhibition brake. IGF-1 action is facilitated by estradiol (E2), which is essential for kisspeptin expression in the preoptic hypothalamic area.Relatively increased IGF-1 and E2 levels in the prepubertal female may prime girls to enter puberty earlier than boys.