Effects of growth hormone and IGF-I on cardiac hypertrophy and gene expression in mice

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 275; no. 2; pp. H393 - H399
• Main Authors: Tanaka, Nobuaki, Ryoke, Tsutomu, Hongo, Minoru, Mao, Lan, Rockman, Howard A, Clark, Ross G, Ross, John, Jr
• Format: Journal Article
• Language: English
• Published: United States 01.08.1998
• Subjects: Actins - biosynthesis; Actins - genetics; Animals; Atrial Natriuretic Factor - biosynthesis; Atrial Natriuretic Factor - genetics; Blood Pressure; Cardiomegaly - physiopathology; Collagen - biosynthesis; Collagen - genetics; Female; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Heart - drug effects; Heart - physiology; Heart - physiopathology; Heart Rate; Heart Ventricles; Hemodynamics - drug effects; Hemodynamics - physiology; Human Growth Hormone - pharmacology; Humans; Insulin-Like Growth Factor I - pharmacology; Mice; Mice, Inbred C57BL; Myocardium - metabolism; Rats; Recombinant Proteins - pharmacology; RNA, Messenger - biosynthesis; Transcription, Genetic - drug effects; Transcription, Genetic - physiology; Ventricular Function, Left
• ISSN: 0363-6135; 0002-9513; 1522-1539
• DOI: 10.1152/ajpheart.1998.275.2.h393

1  Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla 92093; and 2  Genentech, South San Francisco, California 94080 Cardiac hypertrophic and contractile responses were studied in mice administered 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. Also, changes in expression of selected left ventricular (LV) genes in response to IGF-I/GH were compared with those in other forms of cardiac 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 hemodynamic effects; however, IGF-I/GH was synergistic, increasing body weight and LV weights by 39 and 35%, respectively. A measure of myocardial 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 (transverse aortic constriction) or volume overload (arteriovenous fistula) for 2 wk; LV weights were then matched to those in the IGF-I/GH group, and mRNA levels of selected markers were assessed. In contrast to the increased mRNA levels of atrial natriuretic factor, -skeletal actin, and collagen III generally observed in overloaded hearts, changes in IGF-I/GH-treated mice were not significant. Thus high-dose IGF-I/GH produce cardiac hypertrophy and a positive inotropic effect without causing significant changes in expression of fetal and other selected myocardial genes, suggesting that this hypertrophy may be of a more physiological type than that due to mechanical overload. insulin-like growth factor I; myocardial contractility; pressure overload; volume overload; messenger ribonucleic acid; mouse left ventricle; atrial natriuretic peptide