Regulation of neuronal and endothelial nitric oxide synthase by anabolic-androgenic steroid in skeletal muscles.

Karina Fontana, Thalita Rocha, Maria Alice da Cruz-Höfling

Department of Histology and Embryology, Institute of Biology, State University of Campinas, Campinas, SP, Brazil.

Histology and histopathology 2012 Nov

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Anabolic-androgenic steroids (AAS) and exercise share comparable effects on myogenic differentiation, force development, fiber growth and skeletal muscle plasticity. The participation of nitric oxide synthase (NOS) on these effects was only demonstrated in response to exercise. Using immunohistochemistry and western blotting we examined the effect of AAS on the expression of NOS I and III isoforms in three muscles, distinct metabolically and physiologically: soleus (SOL), tibialis anterioris (TA) and gastrocnemius (GAS). Mice with a lipid profile akin to humans were used. Sedentary mice (Sed-C) or exercised, submitted to six-weeks of aerobic treadmill running (one hour/day, 5 days/week) were administered mesterolone (Sed-M and Ex-M, respectively) or gum arabic (vehicle, Ex-C) during the last three weeks, three alternate days per week. Consistently, The TA showed the strongest labeling and the SOL the weakest with NOS III predominating over NOS I. Mesterolone administered to sedentary mice (Sed-C x Sed-M) significantly upregulated NOS I in TA and SOL and NOS III in all three muscles. Mesterolone administered to exercised mice (Ex-C x Ex-M) upregulated NOS I in all three muscles and NOS III in TA and SOL. The exercise to mesterolone-treated mice (Sed-M x Ex-M) produced a strong increase in NOS I expression in GAS; in contrast it antagonized the mesterolone-induced upregulation of NOS I in TA muscle and NOS III in SOL and GAS. The data show nitric oxide (NO) as a potential signaling mediator of AAS effects in skeletal muscle and that NOS I and NOS III upregulations were muscle phenotype-specific. These may be regarded as an indication of the complex NOS/NO signaling mechanism related with AAS effects vs. metabolic/physiological muscle characteristics.

Citation

Karina Fontana, Thalita Rocha, Maria Alice da Cruz-Höfling. Regulation of neuronal and endothelial nitric oxide synthase by anabolic-androgenic steroid in skeletal muscles. Histology and histopathology. 2012 Nov;27(11):1449-58