7 Somatomedin activity in disorders of nutrition and metabolism

Abstract

The existence of the somatomedin peptides was originally hypothesized to explain questions based on studies of growth hormone (GH) action (Salmon and Daughaday, 1957). The demonstration of serum factors which appeared GH-responsive and stimulated growing cartilage in vitro provided evidence for such mediators of GH effects. Subsequent measurements of somatomedins in disorders of the GH axis (GH deficiencyacromegaly) further supported the hypothesis by showing a general correlation with circulating levels of GH. However, extension of somatomedin measurements to other conditions suggested that somatomedins might be regulated by other mechanisms as well. Situations of 'no growth despite GH' and 'growth without GH' were found in which circulating somatomedins or somatomedin activity appeared to parallel levels of insulin and nutritional status more closely than levels of GH (Table 1). Thus, in kwashiorkor and diabetes, growth may be poor despite normal to elevated levels of GH (Hansen and Johansen, 1970; Grant et al, 1973); in these conditions, low levels of somatomedin activity appear to parallel insulin and nutrition more than GH. Conversely, children who are obese or who have had hypothalamic surgery may grow well despite low levels of GH (Van den Brande and Du Caju, 1974; Costin et al, 1976); in such conditions, normal levels of somatomedin activity again appear to parallel levels of insulin and nutrition more than levels of GH. In combination, such observations indicate that somatomedins -- and growth -- are modulated by insulin and nutrition as well as by GH. In view of the anabolic insulin-like actions of the somatomedin peptides (Phillips and Vassilopoulou-Sellin, 1980), such non-GH regulation suggests that somatomedin mechanisms may play an important role in diverting calorie use toward or away from 'growth' as a reflection of nutritional/ hormonal status. While a number of tissues appear to be able to generate somatomedins de novo under tissue culture conditions, the best evidence to date indicates that non-GH regulation of circulating somatomedin activity occurs in the liver.