Alterations of protein metabolism in acromegaly

Purpose of review Growth hormone is a powerful anabolic hormone necessary for normal growth, but its importance in maintaining the cellular and protein mass in adult life is still unclear. However, it is viewed as a drug capable of combating the tissue loss and some metabolic derangements of aging. Growth hormone excess causes acromegaly, a disease characterized by overgrowth of some tissues and multiple metabolic abnormalities. The purpose of this article is to review recent knowledge in acromegaly considering it as a model for clarifying aspects of growth hormone action on body composition, protein dynamics and molecular mechanisms in adult life. Recent findings Acromegaly induces well-documented changes in body fat (decreased), and bone density and water retention (increased), but there are less-clear changes in protein and body cell-mass accretion. Recent studies related insulin resistance to glucose metabolism to accelerated fat oxidation and described the reversibility of such alterations after surgical or pharmacologic therapy. Less attention was paid to changes in protein metabolism. Acromegalics are profoundly insulin-resistant to the antiproteolytic action of insulin, but amino acids are channelled towards protein synthesis because they are still normally spared from oxidation by insulin. This insulin resistance persists months after the surgical cure of acromegaly when glucose metabolism is already normalized. Recent studies suggested that increased use of fat for fuel by growth hormone may also promote protein anabolism and reduce amino acid oxidation. Summary Despite important advances in understanding molecular mechanisms in acromegaly, the specific effects on body cell and protein mass and the specific modulation of local protein dynamics remain poorly defined.