3). Western blot analysis showed darker bands for Pax7 protein in mesterolone-treated group than in control group (Fig. 4A). The mean density of Pax7 bands was significantly (P < 0.05) higher by approximately 19% in mesterolone-treated group than in control group (Fig. 4B). This indicates a greater expression of Pax7 protein in the pectoralis muscle of mesterolone-treated chickens compared to control chickens. This study is the first to demonstrate the effects of the oral steroid mesterolone on the distribution of SCs and myonuclei within avian skeletal muscle. The study reveals AZD9291 ic50
that administration of mesterolone over a period of 4 weeks can significantly increase the number of SCs in the chicken pectoralis muscle. This is also accompanied by increases in the myonuclear number and DNA content. The study shows that mesterolone supplementation increases muscle mass and fiber size (hypertrophy) of chicken pectoralis without exercise. This is comparable to previously reported findings in mouse skeletal muscle (Fontana et al.,2010). The exact mechanism by selleck inhibitor
which mesterolone induces its anabolic effects has not yet been determined. As mesterolone binds strongly to androgen receptors (Kicman,2008), it may act directly through binding to these receptors in both SCN and myonuclei. However, mesterolone may also act indirectly by increasing the level of free endogenous testosterone. This could possibly happen by competing with endogenous testosterone for binding to certain sex hormone binding proteins in the circulation leading to an increase in serum concentration of free endogenous testosterone (Saartok et al.,1984). In addition, mesterolone has a high binding affinity for the enzyme aromatase that converts other steroids into estrogen YES1
(Brueggemeier,1994), even though it does not undergo ring aromatization to estrogen (El-Sadr et al.,1990). It is likely that mesterolone prevents the conversion of other steroids, especially testosterone, to estrogen by blocking the binding site of aromatase enzyme. This study supports the direct action of mesterolone through interaction with androgen receptors, since the model used here was the female chicken, in which insignificant amounts of endogenous testosterone are present. Mesterolone administration leads to significant increases in all SC indices including frequency, number per millimeter of fiber, and concentration. This is similar to our previous findings for the AAS nandrolone decanoate (Allouh and Rosser,2010) and indicates that chemically different steroids with different properties might have similar effects on SCs. To solidify our findings for the effects of mesterolone on SCs, we also investigated the influence of mesterolone on Pax7 protein expression, since Pax7 is specifically expressed by SCs in the muscle tissue (Allouh et al.,2008).