The Journal of Nutrition Vol. 128 No. 2 February 1998, pp. 340S-341S

The Roles of Nutrition, Development and Hormone Sensitivity in the Regulation of Protein Metabolism: An Overview^1,2,3

Teresa A. Davis⁴ and Peter J. Reeds

United States Department of Agriculture, Agricultural Research Service, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030

	INTRODUCTION

Introduction References

Precise regulation of protein synthesis and degradation is essential for achieving net protein accretion during prenatal and postnatal life and for maintaining protein mass during the aging process. Recent evidence, presented in this symposium, suggests that these processes are regulated nutritionally, by changes in the concentrations of amino acids and glucose, and hormonally, via changes in the circulating level of or tissue response to insulin, insulin-like growth factor-I and growth hormone. Disruption of the interplay of these regulatory factors by the stress imposed by trauma and disease affects protein status; the presence of additional quantities of these factors can promote protein deposition. These regulatory factors appear to have the following effects: 1) specifically affect either protein synthesis or degradation; 2) affect individual tissues differently; 3) play different roles at different stages of the life cycle; and 4) interact with each other to regulate protein turnover precisely.

The anabolic drive to promote protein deposition is most potent during periods of life in which growth is most rapid, i.e., fetal and early postnatal life. These stages of life are accompanied by rapid rates of protein turnover to support the high rate of protein deposition. The hormone, insulin, is commonly regarded as an important promoter of fetal growth. Although the stimulation of protein anabolism by insulin during adulthood appears to be due to a suppression of proteolysis, studies presented in this symposium suggest that whole-body proteolysis is relatively resistant to suppression by insulin in the fetus (Liechty and Denne 1998). Furthermore, substrate supply, particularly that of glucose, was demonstrated to be an important regulator of protein anabolism in the fetus via its ability to suppress amino acid oxidation.

During the neonatal period, insulin appears to stimulate protein accretion by promoting the efficient disposal of dietary amino acids as body protein (Davis et al. 1998). This response to insulin decreases with development. The enhanced stimulation of amino acid disposal by insulin in the neonate can be attributed in part to a stimulation of skeletal muscle protein synthesis. On the other hand, amino acid supply, rather than insulin, appears to be an important regulator of liver protein synthesis in the neonate.

Studies presented in this symposium suggest that the decline in protein mass that commonly occurs with aging is due in part to a reduction in the synthesis of specific muscle proteins (Proctor et al. 1998). This reduction is associated with a decline in the levels and actions of anabolic hormones including growth hormone, insulin-like growth factor-I, testosterone and dihydroepiandrosterone. On the basis of the work described, it appears that hormone replacement therapy has the potential to ameliorate the sarcopenia of aging.

Hormone therapy also has been used as an adjunct to the nutritional therapies used to treat patients with protein-wasting diseases. Studies examining the effect of growth hormone on protein metabolism in AIDS patients were presented in this symposium (Garlick et al. 1998). The results suggest that AIDS patients are resistant to the anabolic effects of growth hormone treatment and that this resistance increases with the progression of the disease.

Growth-modifying agents such as somatotropin (growth hormone) and -adrenergic agonists have been demonstrated to enhance protein deposition in livestock (Bell et al. 1998). This increase in protein accretion appears to be due primarily to an increase in protein synthesis, although some evidence suggests than a reduction in protein degradation may also play a role. Nutritional status plays a critical role in maintaining an adequate metabolic state in which the animal can respond to exogenous metabolic modifiers.

Thus, studies presented in the symposium, "The Roles of Nutrition, Development, and Hormone Sensitivity in the Regulation of Protein Metabolism," at Experimental Biology 97, April 7, 1997, New Orleans, LA, demonstrated that the roles of nutrition, hormones and growth factors in the regulation of protein metabolism change with development. The ability of hormones and growth factors to promote protein accretion has led to studies that have demonstrated the potential for the application of these agents as therapeutic intervention in trauma and disease states and in the promotion of growth in livestock.

	ACKNOWLEDGMENTS

The authors thank L. Loddeke for editorial review.

	FOOTNOTES

	LITERATURE CITED

Introduction References

• Bell A. W., Bauman D. E., Beermann D. H., Harrell R. J. Nutrition, development and efficacy of growth modifiers in livestock species. J. Nutr. 1998; 128:360S-363S
• Davis T. A., Burrin D. G., Fiorotto M. L., Reeds P. J., Jahoor F. Role of insulin and amino acids in the regulation of protein synthesis in the neonate. J. Nutr. 1998; 128:347S-350S
• Garlick P. J., McNurlan M. A., Bark T., Lang C. H., Gelato M. C. Hormonal regulation of protein metabolism in relation to nutrition and disease. J. Nutr. 1998; 128:356S-359S
• Liechty E. A., Denne S. C. Regulation of fetal amino acid metabolism: substrate or hormonal regulation? J. Nutr. 1998; 128:342S-346S
• Proctor D., Balagopal P., Nair K. S. Age-related sarcopenia is associated with reduced synthetic rates of specific muscle proteins. J. Nutr. 1998; 128:351S-355S

0022-3166/98 $3.00 ©1998 American Society for Nutritional Sciences