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| Author(s): |
Karina Fontana
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas |
| Defense date: | 2008-08-29 |
| Examining board members: |
Maria Alice da Cruz Hofling;
Heloisa Sobreiro Selistre de Araujo;
Nivaldo Antonio Parizotto;
Humberto Santo Neto;
Denise Vaz de Macedo
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| Advisor: | Maria Alice da Cruz Hofling |
| Abstract | |
The abuse of anabolic-androgenic steroids (AAS) to improve physical performance is associated with serious adverse effects sometimes fatal, however benefits can be gain by its therapeutic controlled use. The present study aimed to evaluate the effects of the use of the anabolic androgenic steroid mesterolone (M, 17 beta-hydroxy-1 alpha methyl-5 alpha-androstan-3-one, C20H32O2) in the soleus (SOL), tibialis anterior (TA) and gastrocnemius (GAS), in the Achilles tendon and in the cardiac muscle remodeling and lipemic profile of transgenic mice (CETP+/-LDLr-/+), sedentary or submitted to a treadmill running aerobic exercise program. Experimental groups of male mice (aged 8 weeks at the beginning of the experiments) sedentary or exercised (6 weeks involuntary treadmill running, average of 16 m/min, 50 min/day, 5 days/week) were treated with mesterolone dissolved in gum arabic (vehicle), or with the vehicle (both at 2 µg/g body weight administered orally - supra physiological dose) in the last three weeks. The animals were weighed every week and the muscles were weighed after sacrifice of the animals. The arterial blood pressure was measured by tail-cuff plethismographys weekly. The delineation of the fibers types was done in the SOL, TA and GAS muscles through the m- ATPase reaction. The myotrophic action of mesterolone, exercise, or both combined, were also determined in relation to fiber types. The number of myofibers, the crosssectional area of the myofibers, and mitochondria, the density of mitochondria/area of myofiber, the number of capillaries/myofiber, the presence of activated satellite cells, split fibers and the morphology of the muscle spindles and of muscle tissue in general were evaluated by light and electron microscopy. The expression of the neuronal (NOS I) and endothelial (NOS III) nitric oxide synthase isoforms was investigated through immunohistochemistry and immmunoblotting. As part of the musculoskeletal system, the Achilles tendon response was evaluated in regard to the collagen synthesis, quantification of hydroxyproline, collagen fibers diameter and area (relative) and ultrastructure of the tendon fibroblasts (tenocytes). Finally, the investigation focused on the cardiac muscle remodeling and quantitative, morphological and biochemical approaches were employed for evaluating the cardiac plasticity and the lipid profile from this transgenic murine model whose lipid profile was transgenically modified to be more close to the human lipid profile. · The results showed that the soleus, tibialis anterior and gastrocnemius muscles respond differentially to the mesterolone treatment, to the aerobic exercise or both in association. Seemingly, fiber type I and the several types of II fibers showed variability. Depending on the muscle to which they belong to they can be recruited, not be recruited or be recruited differentially. Likewise, different degrees of hypertrophy, or absence of hypertrophy can be displayed by a given fiber type depending on the muscle. Similarly, the expression of the nitric oxide synthases, NOS I and NOS III, can be modulated differentially depending on the treatment and muscle analyzed. The association of mesterolone treatment and intense physical exercise can generate synergic or antagonistic effects. · The results showed that mesterolone, physical exercise or both combined were able to increase the hydroxyproline content, the diameter and area of tendon collagen fibrils (contained in an area probe), and to show evidences of increased synthesis of proteins by the fibroblasts, which besides showed several long and slender processes in agreement with characteristics of hypertrophy and enhancement of the synthetic machinery. · The results showed that mesterolone alone induced a pro-atherogenic profile and a pathogenic cardiac hypertrophy. The exercise counteracted these effects and modified favorably both the lipoprotein profile and the cardiac remodeling. (AU) | |