The effect of flutamide on the physical working capacity and activity of some of the key enzymes for the energy supply in adult rats

Abstract

The aim of the study was to assess the effects of androgen receptor antagonists on the physical working capacity and activity of some of the key muscle enzymes for the energy supply in rats. Young adult male Wistar rats were divided into two groups. One group received 15 mg kg−1 of flutamide daily for 6 days a week and the other group served as control for 8 weeks. At the beginning and at the end of the experiment, all rats were subjected to submaximal running endurance (SRE), maximum time to exhaustion (MTE), and maximal sprinting speed (MSS) tests. At the end of the trial, maximum oxygen consumption (VO2max) test was performed and the levels of testosterone, erythrocytes, hemoglobin as well as enzyme activity of succinate dehydrogenase (SDH), lactate dehydrogenase (LDH), and NAD.H2-cytochrome-c reductase (NAD.H2) of the gastrocnemius muscle were measured. Serum testosterone of the flutamide-treated rats was higher than that of the controls, which verifies the effectiveness of the dose chosen. MTE and SRE of the anti-androgen-treated group were lower compared with the initial values. Flutamide treatment decreased the activity of SDH and NAD.H2 compared with the controls. We found no effect of the anti-androgen treatment on MSS, VO2max, running economy, LDH activity, and hematological variables. Our findings indicate that the maintenance of the submaximal and maximal running endurance as well as the activity of some of the key enzymes associated with muscle oxidative capacity is connected with androgen effects mediated by androgen receptors.

Crucial role of androgen receptor in resistance and endurance trainings-induced muscle hypertrophy through IGF-1/IGF-1R- PI3K/Akt- mTOR pathway

“…In addition, flutamide is considered to inhibit AR singling through blocking AR's binding to its ligand like testosterone or dihydrotestosterone [29] , and in the current study flutamide was found to reverse the training-induced increases of AR in muscles, suggested that flutamide might inhibit AR signaling through down-regulating the protein level of AR in tissue, except for the well-known blockade of binding with testosterone. Similar result was reported by a recent study which revealed the inhibitive function of flutamide by down-regulating AR protein in tissues [10] .…”

“…But most of the reports about AR's role were focused on the sedentary participants. At training state, AR was likely to be very important not only for muscle hypertrophy but also strength promotion, for example, the submaximal running endurance and the maximum time to exhaustion were reduced in flutamide-treated rats [10] and in human, the intramuscular AR content influenced the cross-sectional areas of muscle in previously trained men [11] . Although muscle hypertrophy is a vital factor to enhance exercise performance, the roles of AR in exercise-induced muscle hypertrophy are not fully clarified, let alone the underlying molecular mechanisms.…”

“…On the contrary, global AR gene knockout (ARKO) and specific skeletal muscle tissue ARKO mice showed alterations in the muscle mass (such as gastrocnemius, quadriceps and soleus) [5,6] , muscle glycogen [7] and exercise performance. The important role of AR in the increases of muscle mass and exercise performance at untrained state was demonstrated [5,[8][9][10][11] , but whether AR exerted crucial role in exercise-induced muscle hypertrophy in vivo have not been thoroughly verified. To our best knowledge, until now no ARKO model mice have been used to explore AR's role in exercise-induced changes in muscle mass and performance, moreover, ARKO mice could not be obtained commercially.…”

Crucial role of androgen receptor in resistance and endurance trainings-induced muscle hypertrophy through IGF-1/IGF-1R- PI3K/Akt- mTOR pathway

“…But most of the reports about AR's role were focused on the sedentary participants. At training state, AR was likely to be very important not only for muscle hypertrophy but also strength promotion, for example, the submaximal running endurance and the maximum time to exhaustion were reduced in flutamide-treated rats [10] and in human, the intramuscular AR content influenced the cross-sectional areas of muscle in previously trained men [11]. Although muscle hypertrophy is a vital factor to enhance exercise performance, the roles of AR in exercise-induced muscle hypertrophy are not fully clarified, let alone the underlying molecular mechanisms.…”

“…On the contrary, global AR gene knockout (ARKO) and specific skeletal muscle tissue ARKO mice showed alterations in the muscle mass (such as gastrocnemius, quadriceps and soleus) [5,6], muscle glycogen [7] and exercise performance. The important role of AR in the increases of muscle mass and exercise performance at untrained state was demonstrated [5,[8][9][10][11], but whether AR exerted crucial role in exercise-induced muscle hypertrophy in vivo have not been thoroughly verified. To our best knowledge, until now no ARKO model mice have been used to explore AR's role in exercise-induced changes in muscle mass and performance, moreover, ARKO mice could not be obtained commercially.…”