EFFECTS OF GROWTH-HORMONE AND IGF-I ON CARDIAC-HYPERTROPHY AND GENE-EXPRESSION IN MICE

Cardiac hypertrophic and contractile responses were studied in mice ad ministered growth hormone (GH) and insulin-like growth factor (IGF-I) (8 mg.kg(-1).day(-1)), alone or in combination (IGF-I/GH), for 2 wk. A lso, changes in expression of selected left ventricular (LV) genes in response to IGF-I/GH were compared with those in other forms of cardia c hypertrophy. GH or IGF-I alone at three to four times the usual dose in rats failed to produce increases in heart and LV weights and hemod ynamic effects; however, IGF-I/GH was synergistic, increasing body wei ght and LV weights by 39 and 35%, respectively. A measure of myocardia l contractility (maximal first derivative of LV pressure, catheter-tip micromanometry) was increased by 34% in the IGF/GH group, related in part to a force-frequency effect, since the heart rate increased by 21 %. Other mice were treated surgically to produce pressure overload (tr ansverse aortic constriction) or volume overload (arteriovenous fistul a) for 2 wk; LV weights were then matched to those in the IGF-I/GH gro up, and mRNA levels of selected markers were assessed. In contrast to the increased mRNA levels of atrial natriuretic factor, alpha-skeletal actin, and collagen III generally observed in overloaded hearts, chan ges in IGF-I/GH-treated mice were not significant. Thus high-dose IGF- I/GH produce cardiac hypertrophy and a positive inotropic effect witho ut causing significant changes in expression of fetal and other select ed myocardial genes, suggesting that this hypertrophy may be of a more physiological type than that due to mechanical overload.