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: 25.7 x 10(6) (0.09), controls: 19.3 x 10(6) (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.