Insulin-like growth factor 1 (IGF-1): a growth hormone

Abstract

Aim: To contribute to the debate about whether growth hormone (GH) and insulin-like growth factor 1 (IGF-1) act independently on the growth process.

Methods: To describe growth in human and animal models of isolated IGF-1 deficiency (IGHD), such as in Laron syndrome (LS; primary IGF-1 deficiency and GH resistance) and IGF-1 gene or GH receptor gene knockout (KO) mice.

Results: Since the description of LS in 1966, 51 patients were followed, many since infancy. Newborns with LS are shorter (42-47 cm) than healthy babies (49-52 cm), suggesting that IGF-1 has some influence on intrauterine growth. Newborn mice with IGF-1 gene KO are 30% smaller. The postnatal growth rate of patients with LS is very slow, the distance from the lowest normal centile increasing progressively. If untreated, the final height is 100-136 cm for female and 109-138 cm for male patients. They have acromicia, organomicria including the brain, heart, gonads, genitalia, and retardation of skeletal maturation. The availability of biosynthetic IGF-1 since 1988 has enabled it to be administered to children with LS. It accelerated linear growth rates to 8-9 cm in the first year of treatment, compared with 10-12 cm/year during GH treatment of IGHD. The growth rate in following years was 5-6.5 cm/year.

Conclusion: IGF-1 is an important growth hormone, mediating the protein anabolic and linear growth promoting effect of pituitary GH. It has a GH independent growth stimulating effect, which with respect to cartilage cells is possibly optimised by the synergistic action with GH.

Figure 1

The cascade of the growth hormone axis. CNS, central nervous system; GH, growth hormone; GHBP, GH binding protein; GH-S, GH secretagogues; IGF-1, insulin-like growth factor 1; IGFBPs, IGF binding proteins; +, stimulation; –, inhibition.

Figure 2

Type 1 insulin-like growth factor receptor gene and mRNA. Reproduced with permission from Werner.

Figure 3

Resemblance between the insulin and insulin-like growth factor 1 (IGF-1) receptors.

Figure 4

Paracrine insulin-like growth factor 1 (IGF-1) secretion and endocrine IGF-1 targets in the various zones of the epiphyseal cartilage growth zone.

Figure 5

Growth velocity before and during insulin-like growth factor 1 (IGF-1) treatment. Note that in infancy, when the non-growth hormone/IGF-1 dependent growth velocity is relatively high (but low for age), the change induced by IGF-1 administration is less than in older children.