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Cardiovascular Research 2007 76(3):400-408; doi:10.1016/j.cardiores.2007.06.026
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Copyright © 2007, European Society of Cardiology

Growth hormone increases the proliferation of existing cardiac myocytes and the total number of cardiac myocytes in the rat heart

Annemarie Brüela,d,*, Tue E.H. Christoffersenb and Jens R. Nyengaardc

aDepartment of Connective Tissue Biology, Institute of Anatomy, Building 1233, University of Aarhus, 8000 Aarhus C, Denmark
bLaboratory for Molecular Cardiology, Rigshospitalet, Copenhagen, Denmark
cStereology and Electron Microscopy Research Laboratory and MIND Center University of Aarhus, Denmark
dDepartment of Pathology, Aarhus University Hospital, Aarhus, Denmark

*Corresponding author. Tel.: +45 8942 3022; fax: +45 8613 7539. mb{at}ana.au.dk

Objective Growth hormone (GH) is known to induce growth of the normal rat heart. Whether this growth is due solely to hypertrophy of the cardiac myocytes or whether a concomitant hyperplasia of the cardiac myocytes also takes place is currently not known. Therefore, the aim of the present study was to investigate whether GH induces hyperplasia in the left ventricle (LV) of sexually mature rats.

Methods Three-month-old female Wistar rats were injected with GH (5 mg/kg/d) for 80 days, whereas a control group was injected with saline. Before perfusion–fixation, haemodynamic measurements were obtained. Isotropic, uniformly random sections were cut from the isolated LV, and the total number of myocyte nuclei and the average number of nuclei per myocyte were estimated using unbiased stereology. Immunohistochemistry was performed in order to detect proliferation (Ki-67), apoptosis (activated caspase-3), and stem cells (c-kit).

Results GH increased the total number of cardiac myocytes by 33% [GH: 25.7x106 (0.09), controls: 19.3x106 (0.14), P<0.01, (mean (CV)], and this was accompanied by an increase in the percentage of Ki-67 positive myocytes by 216% [GH: 0.0179% (0.65), controls: 0.0057% (1.43), P<0.05]. No significant differences were found for caspase-3 positive or c-kit positive myocytes. GH increased insulin-like growth factor I (IGF-I) content of the myocardial tissue by 754% [GH: 247 ng/g wet weight (0.75), controls: 29 ng/g wet weight (0.58), P<0.01] and the LV wet weight by 50% [GH: 849 mg (0.15), controls: 567 mg (0.07), P<0.001], but did not influence the haemodynamic parameters.

Conclusion These results strongly suggest that GH is able to stimulate cardiac myocytes to re-enter the cell cycle, divide, and thereby increase the number of cardiac myocytes in sexually mature rats.

KEYWORDS Myocyte; Hypertrophy; Histo(patho)logy; Hormones; Growth factors


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