The role of the GH-IGF-I axis in the regulation of myocardial growth: from experimental models to human evidence.

摘要: Growth hormone (GH) is a peptide synthesized and secreted by the anterior pituitary gland. In normal conditions, its synthesis secretion are strictly regulated integrated coordinated actions of two hypothalamic neurohormones: GH releasing factor inhibiting (i.e., somatostatin). The ratio between these factors represents basic dynamic mechanism which neurologic as well extraneurologic influences may functionally affect under physiologic or pathophysiologic conditions (1). Biological effects mediated interaction with specific transmembrane receptor (GHR), expressed in almost all cellular types. As consequence GH–GHR on target tissues, exert direct metabolic effects. However, most relevant biological indirect to large extent stimulation expression insulinlike growth factor-I (IGF-I), liver (endocrine action) peripheral tissues (autocrine/paracrine action). Only small amount liver-derived IGF-I circulates free hormone, responsible for actions. Indeed, bulk circulating bound carrier proteins, called IGF-binding proteins (IGF-BPs), important seems be IGF-BP-3, since it binds more than 95% blood (1, 2). Furthermore, IGF-I/ IGF-BP-3 dimer forms complex another protein subunit, acid-labile this ternary has serum half-life many hours. Both subunit principally liver, their concentrations influenced levels. IGF-BPs serve not only transport circulation, but also prolong half-life, modulate tissue specificity, potentiate neutralize Moreover, number studies have shown that modify variety mammalian cells. relative importance versus locally produced anabolic growth-promoting recently been addressed Sjogren et al. Yakar (3, 4). By using novel tissuespecific recombinant system, groups independently concluded that, although hepatic major contributor levels, crucial postnatal growth, providing evidence an autocrine/paracrine role IGF-I. scenario, body accumulated support concept GH–IGF-I axis targets heart (5–9). particular, demonstrated GHRs largely myocardium (9) interacting GH, they stimulate local biosynthesis IGF-I, act autocrine paracrine manner binding specifically high-affinity membrane-associated (Fig. 1). regard, myocardial content parallel levels (5–8). Studies both animals humans provided consistent involved regulation structure function. consistently critically cardiomyocyte growth.