Human conditions of insulin-like growth factor-I (IGF-I) deficiency

Abstract

Insulin-like growth factor I (IGF-I) is a polypeptide hormone produced mainly by the liver in response to the endocrine GH stimulus, but it is also secreted by multiple tissues for autocrine/paracrine purposes. IGF-I is partly responsible for systemic GH activities although it possesses a wide number of own properties (anabolic, antioxidant, anti-inflammatory and cytoprotective actions). IGF-I is a closely regulated hormone. Consequently, its logical therapeutical applications seems to be limited to restore physiological circulating levels in order to recover the clinical consequences of IGF-I deficiency, conditions where, despite continuous discrepancies, IGF-I treatment has never been related to oncogenesis. Currently the best characterized conditions of IGF-I deficiency are Laron Syndrome, in children; liver cirrhosis, in adults; aging including age-related-cardiovascular and neurological diseases; and more recently, intrauterine growth restriction. The aim of this review is to summarize the increasing list of roles of IGF-I, both in physiological and pathological conditions, underlying that its potential therapeutical options seem to be limited to those proven states of local or systemic IGF-I deficiency as a replacement treatment, rather than increasing its level upper the normal range.

Figure 1

Schematic structures of IGFs and their receptors. Resemblances between Insulin and IGFs allow them to cross-interactions by which IGFs are able to bind to their own receptors (preferently) but also to Insulin receptor (IR) with a lower specificity. The hybrid receptor shares components from both IR and IGF-IR. * IGF-II can also interact with IGF-IR, hybrid receptor and insulin receptor, with a lower affinity.

Figure 2

GH/IGF-I axis and targets. Pituitary GH interacts with GH receptors in hepatocytes increasing IGF-I secretion for endocrinological purposes in different organs, although an autocrine/paracrine IGF-I production by those organs is also present.

Figure 3

Lifelong beneficial properties of IGF-I. Evolution of IGF-I circulating levels and its pluripotent roles along different stages of human development and aging.

Figure 4

IGF-I receptor pathway. Activation of IGF-IR leads to a cascade of related molecules involved in previously described actions of IGF-I (survival, cell growth and differentiation, cytoprotection, glucose metabolism, etc).