Influence of Mesterolone on Satellite Cell Distribution and Fiber Morphology within Maturing Chicken Pectoralis Muscle

Abstract

Mesterolone is a synthetic oral anabolic androgenic steroid used to treat hypogonadism. There are frequent reports of mesterolone abuse in human and equine sports to increase muscle mass and strength. However, limited information is available about how this drug exerts its effects on skeletal muscle. Satellite cells (SCs) are mononuclear myogenic stem cells that contribute to postnatal muscle growth and repair. As SC activation and subsequent differentiation to new myonuclei is a major event during muscle hypertrophy, this study investigated the influence of mesterolone on SC distribution within the pectoralis muscle of chickens. Specifically, this study tested the hypotheses that mesterolone induces avian skeletal muscle hypertrophy, and that mesterolone increases the number of SCs in avian skeletal muscle. Robust immunocytochemical techniques and morphometric analyses were used to calculate the numbers of SCs and myonuclei. Also, DNA concentration and Pax7 protein levels were measured to confirm immunocytochemical findings. Mesterolone significantly increased pectoralis mass and fiber size. All SC indices and number of myonuclei increased significantly by mesterolone administration. In addition, greater DNA concentration and Pax7 protein expression were found in mesterolone-treated birds. This study indicates that mesterolone can induce avian skeletal muscle hypertrophy and that this is correlated with increased number of SCs. We suggest that SCs are key cellular intermediaries for mesterolone-induced muscle hypertrophy. Anat Rec,

Myogenic regulatory factors: The orchestrators of myogenesis after 30 years of discovery

“…4 SCs are mononuclear cells located between the basal lamina and plasmalemma of the skeletal muscle fiber. 3,5 These cells induce muscle growth either by fusing to preexisting myofibers (hypertrophy) or, less commonly, by fusing together to form new myofibers (hyperplasia). [5][6][7] Surprisingly, studies on non-SCs were the first to reveal the molecular mechanisms of the myogenic program.…”

“…3,5 These cells induce muscle growth either by fusing to preexisting myofibers (hypertrophy) or, less commonly, by fusing together to form new myofibers (hyperplasia). [5][6][7] Surprisingly, studies on non-SCs were the first to reveal the molecular mechanisms of the myogenic program. At first, it was noticed that fraction of fibroblast cell line (C3H 10T1/2) was transformed into myogenic lineage cells after being treated with an anti-neoplastic nucleoside analogue, 5-Azacytidine.…”

“…Different stimuli can induce myogenic SC activation such as exercise, 90 electrical stimulation, 91 and some pharmaceutical preparations, notably anabolic androgenic steroids. 2,3,5,6 In general, upon activation, most of SCs gradually downregulate their expression of PAX7 92 and, if present, PAX3. 76 Meanwhile, they begin to upregulate their MRFs as the myogenic program ensues.…”

Differential response of oxidative and glycolytic skeletal muscle fibers to mesterolone

“…A previous study reported that mesterolone significantly increases the weight and fiber size of the soleus muscle of transgenic mice 15 . We found that oral administration of mesterolone significantly increases the number of SCs in maturing avian pectoralis, a response accompanied by increased myonuclear density and DNA content 12 . However, it is unclear if mesterolone has distinct effects on different types of normal adult muscle fibers.…”

“…Among the various stimuli promoting SC activity are anabolic androgenic steroids (AASs), which also augment muscle mass and size 4 , 5 , 12 . Mesterolone (17-beta-hydroxy-1 alpha-methyl-5 alpha-androstan-3-one) is one of the most frequently used exogenous AASs for the treatment of hypogonadism 12 , 13 . Mesterolone is distinguished from other AASs by its unique chemical structure that does not undergo ring aromatization into estrogen therefore it has no estrogenic side effects.…”