Detrimental effects of testosterone on post-myocardial infarction remodelling in female rats.
Clinical data suggest an association of increased serum androgens with cardiovascular mortality in females, but not in males. Therefore, we examined effects of chronic anabolic testosterone administration on left ventricular remodeling after myocardial infarction in female rats. Ovariectomized adult female rats were treated with placebo, supraphysiologic testosterone undecanoate (T), estradiol (E(2)), or T+E(2). Two weeks after ovarcectomy, animals underwent sham-operation or coronary artery ligation. Left ventricular remodeling and function were assessed by echocardiography and hemodynamic investigation. In sham operated animals T administration increased serum T levels and led to cardiac hypertrophy, with an increase in the beta/alpha-MHC-ratio and in IGF-1 expression. After coronary artery ligation, infarct size and mortality were similar among the groups. T treatment aggravated left ventricular hypertrophy and chamber dilatation (end-diastolic diameter, E(2) vs. T vs. E(2)+T, 8.6 +/- 0.6 vs. 9.9 +/- 0.3 vs. 9.8 +/- 0.3 mm, p<0.05) and reduced fractional shortening 8 weeks after myocardial infarction. Extracellular matrix remodeling was not altered by hormonal treatment. In conclusion, chronic anabolic T treatment causes myocardial hypertrophy under basal conditions and adversely affects left ventricular remodeling following myocardial infarction in female rats.
Frantz
S
S
Universität Würzburg, Medizinische Klinik und Poliklinik I, Germany. frantz_s@medizin.uni-wuerzburg.de
Hu
K
K
Widder
J
J
Weckler
B
B
Scheuermann
H
H
Bauersachs
J
J
Ertl
G
G
Callies
F
F
Allolio
B
B
D045930:Anabolic Agents / Q000009:adverse effects*; D000704:Analysis of Variance; D000818:Animals; D004452:Echocardiography; D004958:Estradiol / Q000097:blood / Q000494:pharmacology; D004967:Estrogens / Q000097:blood / Q000494:pharmacology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced* / Q000503:physiopathology; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D010052:Ovariectomy; D012333:RNA, Messenger / Q000096:biosynthesis; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000502:physiology
D045930:Anabolic Agents; D004967:Estrogens; D012333:RNA, Messenger; D013739:Testosterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; C010792:testosterone undecanoate