Growth hormone or somatotropin - Effects of growth hormone
Growth hormone has two mechanisms of action: one direct and another indirect through insulin-like growth factor 1, IGF-1, secretion. Growth hormone activates a cell-surface receptor which in a dimeric form induces signal transduction through many pathways to the nucleus
- Growth hormone itself stimulates lipolysis, which explains why the children defective in growth hormone have an increase in their body fat mass.
- It has a diabetogenic action, by anti-insulin effect, which is observed only after administration of very high doses.
- It elicits a stimulation of cellular differentiation.
- It has an anabolic effect on bone and skeletal muscles less important than that of IGF.
- it induces the release of IGF-1 which is maximum about 20 hours after its administration. It is possible that its apparently direct effect on bone is indirect by inducing a local production of IGF-1 by the bone itself.
Indirect effects by IGF
Growth hormone indirectly activates the synthesis, especially by the liver and to a lesser extent by other organs, of somatomedins called IGF (insulin-like growth factor), IGF-1 and IGF-2, which consist of a linear polypeptide chain of approximately 70 amino acids containing 3 disulfide bonds. IGF-1 was called somatomedin C.
Secreted in plasma, somatomedins are bound to specific transport proteins called IGFBP (insulin-like growth factor binding proteins), IGFBP1 and IGBP2, which could reduce their activity.
The plasma concentrations of IGF-1 and IGF-2 are at a maximum during puberty.
IGF-1 and IGF-2 act on specific receptors of type I and type II. The type I receptor is heterotetrameric consisting of two alpha and two beta subunits, very similar to the insulin receptor, with tyrosine-kinase activity. The type II receptor differs from that of insulin, it is made of only one polypeptide chain and does not have tyrosine-kinase activity.
IGF 1 stimulates growth, protein synthesis and incorporation of glucose, amino acids and sulfate in cells. Its plasma concentration is decreased in patients with dwarfism and is increased in acromegalic patients.
By negative hypothalamic-pituitary feedbach, IGF-1 reduces somatotropin secretion.
IGF-1, obtained by recombinant technology, is available under the name mecasermin, brand name Increlex* and mecasermin rinfabate, brand name Iplex* which is a binary complex of IGF-1 and IGFBP-3 (insulin-like growth factor binding protein-3). Both are given by subcutaneous injection over long-term treatment. IGF-1 is indicated for pediatric patients deficient in IGF-1 despite a normal secretion of GH. When bone growth plates are closed neither GH nor IGF-1 increase statural growth. Hypoglycemia is one of the side effects of IGF-1.