Elegant studies in the last two decades established that the key hormonal axis, the GH-IGF axis, in which GH and IGF-I are produced from early fetal life play a significant role in human linear growth. More recent in vivo and in vitro studies have demonstrated that this axis is composed of hormones with highly specific binding proteins, which modulate their interactions with specific receptors. The development of the IGF system in the first trimester of gestation appears to be GH independent. However, in postnatal life GH is required for IGF-I synthesis and for the normal functional development of growth plate. It has been shown that endocrine, paracrine and autocrine mode of action both of GH and IGFs play important roles in human growth and development.

The "revised somatomedin hypothesis" as described by Le Roith (49) provides the basis for a better understanding of the contribution of systemically secreted and locally acting peptides. However, there are many challenges and interactions at play, with short- and long-term consequences for human growth. Therefore, it is important to appreciate that in addition to the biological and physiological role of our genetic background, of interaction of several hormones and growth factors, other factors such as nutrition and socioeconomic status will have a significant effect in determining the attainment of a normal final height. This phenomenon, known as secular change, has been clearly shown in different populations in the world with a significant difference between current growth pattern and that observed in the early 20th century (95-97).