Effects of growth hormone and IGF-I on cardiac hypertrophy and gene expression in mice.
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, alpha-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.
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- Ventricular Function, Left
- Transcription, Genetic
- Recombinant Proteins
- Rats
- RNA, Messenger
- Myocardium
- Mice, Inbred C57BL
- Mice
- Insulin-Like Growth Factor I
- Humans
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Ventricular Function, Left
- Transcription, Genetic
- Recombinant Proteins
- Rats
- RNA, Messenger
- Myocardium
- Mice, Inbred C57BL
- Mice
- Insulin-Like Growth Factor I
- Humans