Adverse effect of the anabolic-androgenic steroid mesterolone on cardiac remodelling and lipoprotein profile is attenuated by aerobicz exercise training

Abuse of anabolic-androgenic steroids (AAS) for improving physical performance is associated with serious, sometimes fatal, adverse effects. The aim of the present work was to investigate the effects of AAS on the cardiac structure and the plasma lipoprotein profile isolated and in combination with exercise. Transgenic mice with a human lipaemic phenotype (expressing cholesteryl ester transfer protein on the LDL receptor knockout background) were used in this study. Sedentary and exercised mice (treadmill running, five times per week for 6 weeks) were treated with mesterolone (2 mu g/g body weight) or vehicle (control-C) in the last 3 weeks. Four groups were compared: (i) exercise + mesterolone (Ex-M), (ii) exercise + vehicle (Ex-C), (iii) sedentary + mesterolone (Sed-M) and (iv) sedentary + vehicle (Sed-C). Arterial blood pressure and body mass increased in all groups along time, but Sed-M reached the highest values and Ex-C the lowest. Treatment with mesterolone increased total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-c) and very LDL-c (VLDL-c) plasma levels. However, exercise blunted some of these deleterious effects by increasing high-density lipoprotein cholesterol and decreasing LDL-c, VLDL-c and triglycerides. Exercise training induced beneficial effects, such as physiological cardiomyocyte hypertrophy, increase in myocardial circulation and decrease in cardiac interstitium. However, mesterolone impaired such physiological gains and in addition increased troponin T plasma levels both in sedentary and exercised mice. Thus, while mesterolone induced pro-atherogenic lipoprotein profile and pathogenic cardiac hypertrophy, exercise counteracted these effects and modified favourably both the lipoprotein profile and the cardiac remodelling induced by mesterolone.