MesteroloneProviron is considered by some bodybuilders to be dinobots names relatively mild anabolic androgenic steroid mesterolone anabolic by Schering Bayer-Schering. Also known as mesterolone, the steroid is not particularly beneficial in its anabolic or mesterolone anabolic properties. It is perceived by most mesterolone anabolic to exhibit very little estrogenic and progestational activity. However, other undesired Proviron side effects are possible, mesterolone anabolic as:. Proviron mesterolone is sometimes used by athletes during cutting phases. How is it used?
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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. Four groups were compared: Arterial blood pressure and body mass increased in all groups along time, but Sed-M reached the highest values and Ex-C the lowest. 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.
Androgenic—anabolic steroids AASs are synthetic derivatives of the male hormone testosterone. The therapeutic use of AASs is indicated in endocrine dysfunction of the testes, age-related and HIV-related muscle wasting Vermeulen From clinical trials, it seems likely that appropriate prescription of AASs may have positive anabolic effects on cachexia associated with HIV, cancer, burns, renal and hepatic failure and anaemia associated with leukaemia or kidney failure, which overcome the threat of side effects for review, see Basaria et al.
Generally administered in supraphysiological doses, the abuse of AASs by healthy athletes has been connected with the incidence of cardiovascular disease CVD , such as development of hypertension, cardiomyopathy, atrial fibrillation, cerebrovascular accident, myocardial infarction, disturbances in haemostatic system, ventricular thrombosis and systemic embolism and acute heart failure Dickerman et al.
In addition, it has been shown that testosterone may affect negatively the recovery of postischaemic myocardial infarction by activating pro-inflammatory cytokine production Wang et al.
Studies have also shown that the use of AASs induces atherogenic lipoprotein profile with a decrease in high-density lipoprotein cholesterol HDL-c and apolipoprotein Al and an increase in low-density lipoprotein cholesterol LDL-c plasma levels Glazer On the other hand, exercise training has been associated with a reduced risk of CVD, possibly because it leads to an improvement of the lipoprotein profile LaRosa On the other hand, experimental and clinical evidence suggests androgen deficiency as a potential risk factor for CVD for review, see Winkler This transgenic mice model is interesting because its lipoprotein profile is closer to that of the humans than the wild-type mouse.
In the present study, the effects of mesterolone beta-hydroxyalpha-methylalpha-androstanone, C 20 H 32 O 2 , a synthetic steroid with anabolic and androgenic activities, were evaluated for its potency in inducing cardiac structure remodelling and altering lipoprotein profile in this transgenic murine model.
In addition, we verified whether exercise training modulates such effects. Twenty-four adult male mice aged 2 months were divided into four groups of six animals: Gum arabic was used as vehicle given its non-toxic and pro-absorptive effects in small intestine Codipilly et al.
Exercised mice were allowed to adapt to treadmill running for 1 week prior to the use of the experimental protocol. After adaptation, exercised mice were subjected to 6 weeks of intensive exercise training treadmill running , 5 days a week, as scheduled in Table 1 adapted from Smolka et al. Blood pressure BP and BM were monitored weekly prior to any experimental procedure. All animals were habituated to the BP measurement device for 7 days before the onset of the experimental period.
Exercise 6 weeks and anabolic—androgenic steroid AAS or vehicle administration 3 weeks protocol. At the end of the experimental period, overnight fasted mice were deeply anaesthetized with a 1: Blood samples were taken from the right atrium of the heart for plasma lipid analyses. Hearts were removed and the atria were separated from the ventricles and the left ventricle with the interventricular septum LV was weighed and then cut into two halves, put with the sectioned face down and then sectioned perpendicular to the ventral face at random.
For stereology, the myocardium of the LV consisting of cardiomyocytes cmy plus cardiac interstitium int, the latter consisting of connective tissue and intramyocardial vessels, ve was analysed. The stereological analysis used a test system with 36 test points and a known area.
The volume densities of the structures were estimated as: The mean cross-sectional area of the cardiomyocyte A cmy was estimated as: The data were tested for deviations from Gaussian distribution using the Kolmogorov—Smirnov test graph pad prism version 5.
The statistical comparison among the control and treated groups was determined using one-way anova pair-wise followed by the post hoc test of Tukey. In addition, two-way anova was used where appropriate to determine how mesterolone treatment or exercise training affected the results, and whether there was an interaction between these two conditions.
A P -value of 0. Blood pressure tended to increase along the trial period, particularly from the third week onwards in the mesterolone groups highest BP values in both the Sed-M and Ex-M groups. It is noteworthy that exercise training delayed the rhythm of increase of BP in both the mesterolone-treated and vehicle-treated groups.
One-way anova followed by Tukey test. Groups inside rectangles not inter-sectioned to each other present a week-by-week significant difference as follows: Figure 2 shows that BM gain was lower in exercised than in sedentary mice. Because in Ex-C, BM was maintained practically at a constant level since the beginning of the experimental period, a slight, but statistically significant difference was found comparing Sed-M vs. However, the effect of exercise in maintaining low BM gain was not enough to abolish the gain promoted by mesterolone and hence there is no significant difference between Sed-M and Ex-M.
Considering TC plasma levels in the Sed-C group as reference Compared with the Sed-C group These findings indicated that a beneficial effect of the exercise training on the plasma lipids was sufficient to counteract the adverse mesterolone effect.
Very low-density lipoprotein cholesterol did not differ between exercised groups. These results show that exercise associated with mesterolone had an additive effect on LV mass index Figure 4. There was significant difference between Sed-M vs. Exercise training per se decreased the V v int in control mice treated with vehicle whereas increased in the sedentary mice treated with mesterolone Figure 5.
These findings show that exercise training is able to reduce the cardiac interstitium collagen fibre increment. There were significant differences among groups as follows: Ex-C and Sed-M vs. Ex-M and Ex-C vs. These findings indicated that exercise training per se causes cardiomyocyte hypertrophy and exercise training combined with administration of mesterolone enhances this hypertrophy. One-way and two-way anova followed by Tukey test.
Photomicrographs showing the left ventricle myocardium in transgenic mice. Note that qualitatively cardiomyocytes are higher in size in exercised a, b and smaller in sedentary d, c groups. The insets depict a high magnification of cardiomyocytes of Ex-M a and Se-C d. However, no statistical differences were observed in intramyocardial blood vessels of Ex-M and Sed-M groups Figure 8.
Thus, mesterolone treatment blunted the benefit gained by exercise. There was significant difference between Sed-C vs. The highest value was achieved in the Sed-M group 0. In Ex-M mice, the TnT value was 0. On the other hand, the exercise training programme applied to these mice increased the levels of HDL-c and decreased VLDL-c the precursor of LDL-c and TG significantly, both in mice treated with vehicle or mesterolone.
The significant difference in the BM gain and BP produced both by mesterolone and exercise per se taking as reference Sed-C is likely not relevant from the physiological point of view. Regular and moderate exercise training have been associated with a reduced risk of CVD, partially because of an improvement in the lipoprotein profile LaRosa However, the amount of exercise training required to obtain benefits is debatable Blair et al.
In general, only high-intensity exercise training or long-term endurance exercise programme are able to improve overall lipoprotein profile, including elevation of HDL-c and reduction in TG levels in humans Seals et al. On the other hand, studies on the exercise-mediated improvement of lipoprotein profile in mice and rats should be observed with prudence if the aim is to compare with humans, mainly because differences exist in the expression of proteins involved in transport and tissue uptake of lipoproteins.
In this regard, the animal model studied here presented a lipid profile akin to the humans and so lipoprotein response to exercise training is expected to be more feasible in comparison with that in humans. Clinical reports of misuse of AASs by athletes and studies in experimental animals have shown the occurrence of deleterious structural myocardial alterations and heart hypertrophy Bauman et al.
Treatment of rats with supraphysiological doses of AASs induced pathological myocardial hypertrophy, and when combined with exercise, these steroids reduced the beneficial effects of exercise on LV hypertrophy and cardiac circulation Tagarakis et al. In the current study, mesterolone alone Sed-M promoted only slight changes in the cardiac structure, i. On the other hand, the exercise training induced favourable cardiac remodelling either in mice treated with mesterolone or vehicle.
This is evidenced by a marked reduction in the cardiac interstitium more prominent in Ex-C and enlargement of cardiomyocyte size.
Increased levels of circulating TnT, a marker of myocardium lesion, confirm the deleterious effect of mesterolone in sedentary mice and exercise training attenuated this adverse effect of mesterolone on the cardiac integrity.
In addition, the exercise training enhanced significantly the cardiac vascularization in the Ex-C and, to a lesser extent, in Ex-M groups compared with Sed-C. This probably represents a response to the increased myocardial oxygen demand imposed by physical activity. Similar effects of exercise training were observed in a previous study in ovariectomized rats Marques et al. This increase in cardiac vascularization may be of importance in the case of ischaemic events.
Mesterolone treatment of exercised mice suppressed the amelioration of the benefits of physiologic hypertrophy, the improvement of the myocardial circulation and part of the reduction in interstitium induced by the exercise training programme.
Therefore, our findings show the strong adverse effects of mesterolone on plasma lipid and lipoprotein metabolism, which were prevented or attenuated by exercise training in this murine model. On the other hand, our data also show that exercise per se induces beneficial changes in cardiac remodelling and myocardial vascular supply, all of which are totally or partially impaired by the mesterolone use.
The authors thank the Departamento de Anatomia for the use of its facility, Mr. National Center for Biotechnology Information , U. Int J Exp Pathol. Received Mar 3; Accepted Jun This article has been cited by other articles in PMC. Abstract Abuse of anabolic—androgenic steroids AAS for improving physical performance is associated with serious, sometimes fatal, adverse effects.
Experimental protocol Twenty-four adult male mice aged 2 months were divided into four groups of six animals: Table 1 Exercise 6 weeks and anabolic—androgenic steroid AAS or vehicle administration 3 weeks protocol. Open in a separate window. Statistical analysis The data were tested for deviations from Gaussian distribution using the Kolmogorov—Smirnov test graph pad prism version 5.
References Alen M, Rahkila P. Reduced high-density lipoprotein-cholesterol in power athletes: A comparison of body and organ weights, physiologic parameters, and pathologic changes in target organs of rats given combinations of exercise, anabolic hormone, and protein supplementation.