Demonstration of direct effects of growth hormone on neonatal cardiomyocytes.
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.
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C
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Departments of Pediatrics, Molecular Genetics and Biochemistry, and Cardiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Schwartzbauer
G
G
Sperling
M A
MA
Devaskar
S U
SU
Thamotharan
S
S
Robbins
P D
PD
McTiernan
C F
CF
Liu
J L
JL
Jiang
J
J
Frank
S J
SJ
Menon
R K
RK
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D017931:DNA Primers; D013006:Growth Hormone / Q000494:pharmacology*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011986:Receptors, Somatotropin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics
D017931:DNA Primers; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone