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. 2011 Sep;17(9):BR266-73.
doi: 10.12659/msm.881930.

Testosterone-induced hypertrophy, fibrosis and apoptosis of cardiac cells--an ultrastructural and immunohistochemical study

Theodora Papamitsou  1 , Dimitris Barlagiannis, Vasileios Papaliagkas, Eleni Kotanidou, Maria Dermentzopoulou-Theodoridou
Affiliations

Testosterone-induced hypertrophy, fibrosis and apoptosis of cardiac cells--an ultrastructural and immunohistochemical study

Theodora Papamitsou et al. Med Sci Monit. 2011 Sep.

Abstract

Background: Androgen abuse is an increasing problem amongst professional and amateur athletes. Moreover, testosterone, apart from its widely accepted indications, is used for a variety of other indications such as aging and ischemia. Its actions are mainly attributed to a specific genomic mechanism through the androgen receptor, but emerging evidence reveals non-genomic effects as well. The use of androgens has been linked with several adverse effects. The purpose of this study was to examine the effects of testosterone on the morphology and the ultrastructure of the myocardium and to investigate the possible role of apoptosis.

Material/methods: We used 12 adult male Wistar rats, separated into 2 groups. Group A consisted of 6 rats that were administered high doses of testosterone enanthate, while group B consisted of 6 male Wistar rats that received placebo (normal saline) intramuscularly. After the last day of treatment, all rats were anesthetized and sacrificed, and the hearts were removed and processed for optical and electron microscopy and immunohistochemical detection of caspase-3, an apoptosis marker.

Results: We found significant myocardial hypertrophy along with abundant ultrastructural alterations. The immunohistochemical staining of the myocardial cells for caspase-3 was positive in group A (experimental group), which is interpreted as an activation of apoptosis by testosterone treatment.

Conclusions: Testosterone abuse has serious adverse effects, including myocardial hypertrophy, myocardial fibrosis and activation of apoptosis. These findings need to be taken into account whenever androgens are prescribed to improve performance or as hormone therapy.

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Figures

Figure 1
Figure 1
Significant myocardial hypertrophy (experimental Group A). Hematoxylin-Eosin ×25.
Figure 2
Figure 2
The myocardial section from group B (control group) appears normal. Hematoxylin-eosin ×25.
Figure 3
Figure 3
Mitochondria of oedematous morphology (large arrows) and endothelial cytoplasmic foot processes Group A ×12000.
Figure 4
Figure 4
The appearance of the myofibrils and the mitochondria is normal. Group B (control rats) ×15000.
Figure 5
Figure 5
The Z band has curved shape (arrows). There are numerous pinocytoplasmic cysts (small arrows) inside the cytoplasm of the endothelial cell. Group A ×10000.
Figure 6
Figure 6
Oedematous mitochondria, collagen fibres (arrows). There is some degree of intracellular oedema. Group A ×8000.
Figure 7
Figure 7
Between the capillary wall and myocardial cell there are collagen fibres (arrows). The nucleus of the endothelial cell is irregularly shaped (white arrow). Group A ×10000.
Figure 8
Figure 8
Oedematous mitochondria (black arrows), collagen fibres (white arrows). The abundance of pinocytoplasmic cysts is easily noticeable (small arrows). Group A ×10000.
Figure 9
Figure 9
Negative staining of rat myocardial cells of group B. No apoptosis detected in the control rats. ×125.
Figure 10
Figure 10
Positive myocardial staining for caspase-3. This is an indication of the activation of the apoptosis cascade after the administration of testosterone in rats of group A. ×480.
Figure 11
Figure 11
Positive immunostaining of myocardial cells for caspase-3. Group A. ×1200.
Figure 12
Figure 12
RGB colour histograms of microphotographs showing myocardial immunohistochemical staining for caspase-3, determined by ImageJ. (A) Rat myocardial cell in control rats, corresponding to Figures 9. (B, C) Rat myocardial cells in the experimental group, after the administration of testosterone, corresponding to Figures 10, 11.
Figure 13
Figure 13
Myocardial fibrosis induced by testosterone and evaluated by Masson trichrome staining. (A) Indicative heart section from rat of the control group (4×10), fibrosis ratio 1.11±0.15%. (B, C) Heart sections from the experimental group received testosterone (4×40), fibrosis ratio 3.92±0.05% (p<0.01 between the two groups). (D) section of cardiac vein from the experimental group (4×10), fibrosis ratio 4.22±0.32% (p<0.01 between the two groups). Each group n=6. C: Colagen, CC: Cardiac cells, L: lipids, A: Artery.
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