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Updated: Aug 14, 2026
Isolation and Culture of Neonatal Mouse Cardiomyocytes
Published on: September 6, 2013
Demonstration of direct effects of growth hormone on neonatal cardiomyocytes
C Lu1, G Schwartzbauer, M A Sperling
1Departments of Pediatrics, Molecular Genetics and Biochemistry, and Cardiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Insights
Growth hormone (GH) directly stimulates heart cell growth and alters metabolism, independent of insulin-like growth factor 1 (IGF-1). This study establishes a reliable model for investigating GH
Area of Science:
- Cardiology
- Endocrinology
- Molecular Biology
Background:
- The precise mechanisms of growth hormone (GH) action on the heart are not fully understood.
- It remains uncertain if GH's cardiac effects are direct or mediated by insulin-like growth factor 1 (IGF-1).
- Cultured neonatal cardiomyocytes typically lose growth hormone receptors (GHRs), hindering direct study of GH effects.
Purpose of the Study:
- To establish a functional model for studying direct GH effects on cardiomyocytes.
- To investigate the impact of GH on cardiomyocyte size, gene expression, and metabolic pathways.
- To determine the role of IGF-1 in mediating GH's cardiac actions.
Main Methods:
- Neonatal rat cardiomyocytes were infected with adenovirus expressing murine GHR to restore GHR function.
- GH signaling pathways (JAK2/STAT5, MAPK, Akt) were assessed for activation.
- Changes in cardiomyocyte size, expression of specific mRNAs (c-fos, MLC2, alpha-actin, IGF-1, ANF), and metabolic substrate uptake/transport were measured.
Main Results:
- GH stimulation activated JAK2/STAT5, MAPK, and Akt pathways in cardiomyocytes expressing GHR.
- GH significantly increased cardiomyocyte size and expression of c-fos, myosin light chain 2, and skeletal alpha-actin mRNAs.
- GH altered cellular metabolism by increasing leucine and palmitic acid uptake and fatty acid transport protein mRNA, while decreasing 2-deoxy-d-glucose uptake and Glut1 protein levels, without affecting IGF-1 or ANF mRNA.
Conclusions:
- GH directly induces hypertrophy in cardiomyocytes via a model expressing functional GHRs.
- GH significantly alters cardiomyocyte metabolism, suggesting direct effects on substrate utilization.
- These GH-induced cardiac effects occur independently of changes in IGF-1 mRNA levels, indicating a potential IGF-1-independent pathway.
Abstract:
The cellular and molecular basis of growth hormone (GH) actions on the heart remain poorly defined, and it is unclear whether GH effects on the myocardium are direct or mediated at least in part via insulin-like growth factor (IGF-1). Here, we demonstrate that the cultured neonatal cardiomyocyte is not an appropriate model to study the effects of GH because of artifactual loss of GH receptors (GHRs). To circumvent this problem, rat neonatal cardiomyocytes were infected with a recombinant adenovirus expressing the murine GHR. Functional integrity of GHR was suggested by GH-induced activation of the cognate JAK2/STAT5, MAPK, and Akt intracellular pathways in the cells expressing GHR. Although exposure to GH resulted in a significant increase in the size of the cardiomyocyte and increased expression of c-fos, myosin light chain 2, and skeletal alpha-actin mRNAs, there were no significant changes in IGF-1 or atrial natriuretic factor mRNA levels in response to GH stimulation. In this model, GH increased incorporation of leucine, uptake of palmitic acid, and abundance of fatty acid transport protein mRNA. In contrast, GH decreased uptake of 2-deoxy-d-glucose and levels of Glut1 protein. Thus, in isolated rat neonatal cardiomyocytes expressing GHR, GH induces hypertrophy and causes alterations in cellular metabolic profile in the absence of demonstrable changes in IGF-1 mRNA, suggesting that these effects may be independent of IGF-1.
