Growth hormone (GH) is the primary regulator of insulin-like growth factor-I (IGF-I) production in a wide variety of tissues. After secretion by the pituitary GH, GH is transported to the liver and stimulates IGF-I production in the liver. The IGF-I produced in the liver accounts for most of the IGF-I in the circulation. The circulating IGF-I will have effects on extra hepatic tissues as the heart, lung, muscles and kidney. Circulating IGF-I feeds back at the level of the pituitary gland and the hypothalamus to inhibit growth hormone secretion. GH may bypass the liver and directly stimulate IGF-I production in other target organs. In this way GH stimulates locally IGF-I production in an autocrine or paracrine fashion. In addition, in many tissues IGF-I can be locally formed in autocrine and paracrine fashion and induce effects independently from GH. In the circulation IGF-I is almost for 100% bound to the so-called insulin-like binding proteins, the IGFBPs. The IGFBPs have many functions: they act as transport proteins, they prolong half-life of IGF-I in the circulation. Another function of the IGFBPs is the modulating of IGF-I activity. In some situations they will stimulate IGF-I effects, but in some other circumstances they will inhibit/prevent IGF-I actions, and finally by the binding of IGF-I to the IGFBPs the body has a manner to deliver IGF-I in a tissue- and cell-specific way.Why should combination of GH and IGF-I be more effective than GH alone or IGF-I alone? I will give some arguments: 1) Clearance of IGF-I may be markedly altered by the (co)administration of GH, Since GH administration stabilizes the formation of the ternary IGF-binding complex, it potentially will provide sustained action of IGF-I. 2) Higher serum IGF-I levels are achieved with a combination treatment of GH and IGF-I than with GH treatment alone or IGF-I alone. 3) The combination GH and IGF-I counteracts disadvantageous effects on glucose metabolism of either GH alone or IGF-I alone and is synergistic with respect to lipolysis and proteolysis. 4) GH may exert direct actions on tissues independently from IGF-I. 5) The combination of GH and IGF-I may be more effective in improving tissue IGF-I levels, and this latter effect may be more important than increasing serum IGF-I concentrations.
In conclusion, the combination of GH and IGF-I may be more effectively improving tissue IGF-I levels and may have substantially more anabolic actions and a better balanced glycaemic control than GH alone or IGF-I alone.
03 - 07 May 2008
European Society of Endocrinology