Growth Hormone Exerts Much of Its Effect Through Intermediate Substances Called “Somatomedins” (Also Called “Insulin-Like Growth Factors”)
When growth hormone is supplied directly to cartilage chondrocytes cultured outside the body, proliferation or enlargement of the chondrocytes usually fails to occur. Yet growth hormone injected into the intact animal does cause proliferation and growth of the same cells.
In brief, it has been found that growth hormone causes the liver (and, to a much less extent,other tissues) to form several small proteins called somatomedins that have the potent effect of increasing all aspects of bone growth. Many of the somatomedin effects on growth are similar to the effects of insulin on growth. Therefore, the somato-medins are also called insulin-like growth factors (IGFs).
At least four somatomedins have been isolated, but by far the most important of these is somatomedinC (also called IGF-I). The molecular weight ofsomatomedin C is about 7500, and its concentration in the plasma closely follows the rate of growth hormone secretion.
The pygmies of Africa have a congenital inability to synthesize significant amounts of somatomedin C. Therefore, even though their plasma concentration of growth hormone is either normal or high, they have diminished amounts of somatomedin C in the plasma; this apparently accounts for the small stature of these people. Some other dwarfs (e.g., the Lévi-Lorain dwarf) also have this problem.
It has been postulated that most, if not all, of the growth effects of growth hormone result from somatomedin C and other somatomedins, rather than from direct effects of growth hormone on the bones and other peripheral tissues. Even so, experi-ments have demonstrated that injection of growth hormone directly into the epiphyseal cartilages of bones of living animals causes the specific growth of these cartilage areas, and the amount of growth hormone required for this is minute. Some aspects of the somatomedin hypothesis are still questionable. One possibility is that growth hormone can cause the formation of enough somatomedin C in the local tissue to cause local growth. It is also possible that growth hormone itself is directly responsible for increased growth in some tissues and that the somatomedin mechanism is an alternative means of increasing growth but not always a necessary one.
Short Duration of Action of Growth Hormone but Prolonged Action of Somatomedin C. Growth hormone attaches onlyweakly to the plasma proteins in the blood. Therefore, it is released from the blood into the tissues rapidly, having a half-time in the blood of less than 20 minutes. By contrast, somatomedin C attaches strongly to a carrier protein in the blood that, like somatomedin C, is produced in response to growth hormone. As a result, somatomedin C is released only slowly from the blood to the tissues, with a half-time of about 20 hours. This greatly prolongs the growth-promoting effects of the bursts of growth hormone secretion shown in Figure 75–6.
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