NUTRITION AND THE SOMATOTROPH AXIS - FROM MOLECULAR MECHANISMS TO CLINICAL ISSUES

Nutritional factors play, with growth hormone, a cardinal role in the regulation of insulin-like growth factor-I, both in man and in animals . The observation of low IGF-I in face of increased GH secretion or de spite exogenous GH supports the concept that dietary restriction induc es a state of apparent GH resistance. Animal and in vitro models have been developed to investigate the mechanisms responsible for GH resist ance. these mechanisms are multiple and complex. The role of liver GH receptors is related to the severity of the nutritional insult. in sev ere dietary restriction such as fasting, a marked decrease of the numb er of somatogenic receptors supports the role of a receptor defect in the decline of circulating IGF-I. In contrast, in less severe forms of dietary restriction such as protein deprivation, a post-receptor defe ct in the GH action at the hepatic level is responsible for the IGF-I decline. nutritional deprivation decreases IGF-I production by diminis hing IGF-I mRNA levels in the liver, likely through reduced transcript ion rate of the IGF-I gene. This decline in IGF-I gene expression is m ainly caused by nutrient deficiency (amino acids) and less importantly by the nutritionally-induced hormonal changes (insulin). In addition to decreased IGF-I production, dietary restriction also causes an incr ease in the clearance and degradation of serum IGF-I, which contribute s to the reduction of circulating IGF-I. Finally, nutrient deprivation impairs the growth-promoting actions of IGF-I. In humans, both acute dietary and chronic restriction are associated with low serum IGF-I co ncentrations. Both energy and proteins are critical in the regulation of serum IGF-I concentrations. The essential amino acids content of th e diet is also crucial for the optimal restoration of IGF-I after fast ing. Overfeeding is not as potent a stimulus for raising IGF-I as diet ary restriction is for reducing serum IGF-I. Clinical studies suggest that circulating IGF-I is an index or variations of the nutritional st atus, more sensitive and reliable than conventional nutritional marker s (prealbumin, transferrin...).