Clenbuterol treatment affects myosin heavy chain isoforms and MyoD content similarly in intact and regenerated soleus muscles.

AIMS: Pharmacological treatment with the beta2-adrenoceptor agonist clenbuterol is known to induce a slow-to-fast fibre type and myosin heavy chain (MHC) isoform transition in intact muscle. This study examined the sensitivity of regenerated soleus muscle to 4 weeks of clenbuterol treatment (2 mg kg-1 day-1). METHODS: Female Wistar rats were divided into two groups: vehicle treated (n = 8) and clenbuterol treated (n = 8). The clenbuterol effects on MHC and MyoD expression were examined in soleus muscles either intact, or previously degenerated by venom of the Notechis scutatus scutatus snake. RESULTS: Post-treatment body weights and skeletal muscle weights were not affected by clenbuterol treatment. Muscle protein concentration was higher, and body fat lower in clenbuterol-treated rats than in vehicle-treated animals (P < 0.05). Polyacrylamide gel electrophoresis of soleus myofibrillar protein indicated a clenbuterol-induced decrease in the relative percentage of type I MHC with a concomitant increase in type IIa MHC (31%, P < 0.001). No degeneration effect was observed after 28 days of recovery on the MHC isoform content, and regenerated soleus muscles exhibited the same phenotypical profile as intact soleus muscles, whether or not they were treated with clenbuterol. In intact and in regenerated soleus muscles, MyoD protein levels were significantly increased by clenbuterol treatment (90 and 77%, respectively, P < 0.001). CONCLUSION: These results show that regenerated soleus muscles, comprising a homogeneous population of fibres deriving from satellite cells, have a similar response to clenbuterol as intact muscle arising from at least two discrete populations of myotubes; it is suggested that the activity of signalling pathways involved in the effects of clenbuterol on MHC transitions is not related to the developmental history of myofibres.

Effects of hindlimb suspension and androgen treatment on testosterone receptors in rat skeletal muscles.

This study tested the specific and combined effects of testosterone treatment and hindlimb suspension (HS) on the properties of steroid receptors in skeletal muscle. Male rats were either administered weekly high doses of testosterone heptylate (10 mg x kg(-1)) or olive oil placebo, and were either tail-suspended or acted as controls. After 3 weeks of treatment, three muscles were excised from each animal, soleus (SOL), extensor digitorum longus (EDL), and plantaris. The results showed that the testosterone treatment was unable to minimise the HS-induced atrophy of skeletal muscle. As expected, HS altered the fibre-type composition of SOL muscles (-33% of type I, +188% and +161% of type IIa and intermediate fibres respectively, P < 0.01). No overall effect of treatment was detected on the fibre-type composition of either slow or fast-twitch muscles. Binding capacity determined by a radiocompetition technique was increased by HS, especially in SOL and EDL muscles (P < 0.01), while HS or steroid treatment decreased the affinity of the steroid receptors. The combination of HS and testosterone administration resulted in a decrease in binding capacity and affinity of steroid receptors in skeletal muscles. Steroid receptors in fast-twitch muscles exhibited a higher affinity than those in slow-twitch muscles, and it is suggested that it is likely that testosterone treatment is more effective in fast-twitch than in slow-twitch muscles. It was concluded that the lack of preventive effect of testosterone treatment on HS-induced SOL muscle atrophy could be explained by both a decrease in steroid sensitivity and the removal of mechanical factors.

Changes in testosterone muscle receptors: effects of an androgen treatment on physically trained rats.

From results obtained in physiological investigations carried out on various tissues sensitive to androgens, it seems that the hormonal receptivity can reflect changes in the endocrine status and specific response of a tissue. The purpose of the present investigation was to test whether an androgen treatment could modify the receptivity to testosterone of the skeletal muscle and myocardium of endurance trained rats. The experiment extended over 8 weeks, and animals received injections of delayed testosterone heptylate every seven days. The myocardium and two skeletal muscles with opposed functions and typology were examined: the extensorum digitorum longus (EDL), and the soleus (SOL). Results obtained using techniques based upon the radio-competition principles provided information on the testosterone-receptor binding. The binding curves were plotted up to the saturating concentration of tritiated mibolerone, a synthetic androgen specific of androgen receptors. The quantity of receptors, calculated at the specific saturation plateau is expressed in fmol/mg protein. Results show that contractile muscular activity always increased the quantity of receptors whereas the steroid treatment decreased it. Thus for EDL and SOL of control trained rats the quantity of receptors was 0.78 and 0.82 fmol/mg protein, respectively, compared to 0.23 and 0.43 fmol/mg protein for sedentary testosterone-treated rats. The same "contractile activity" effect was observed on the myocardium but enhanced with values of 1.63 fmol/mg protein for control trained rats versus 0.30 fmol/mg protein for sedentary testosterone-treated rats. The receptivity to testosterone of the skeletal muscle and myocardium changes under the effect of an androgen treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Circadian rhythms in plasma levels of cortisol, dehydroepiandrosterone, delta 4-androstenedione, testosterone and dihydrotestosterone of healthy young men.

Three healthy males (18, 22 and 30 years of age; 85 kg/177 cm, 82 kg/181 cm and 75 kg/168 cm, respectively), synchronized with a diurnal activity (06.00 to 23.00 h) and nocturnal rest, volunteered for this study. Blood was sampled (venous catheter) hourly during a 24 h span. A radiocompetition method was used for cortisol determinations. Other steroids were first extracted (ethyl-ether) from each plasma sample, then chromatographed on a celite column to isolate 3 fractions: 1) delta 4-androstenedione (delta-4); 2) dihydrotestosterone (DHT) and dehydroepiandrosterone (DHA); 3) testosterone (T). A radioimmunological assay was used thereafter for the determination of androgenic steroids. Statistically significant (both conventional and cosinor methods) circadian rhythms were detected (P > 0.005). Acrophases (peak times) occurred in the following order: cortisol (07.28), DHA (08.43), delta-4 (09.54), T (11.15) and DHT (16.37). The respective circadian amplitudes of DHA and delta-4 were smaller than those of cortisol while the amplitudes T and DHT did not show differences statistically significant from each other.

Plasma variations in testicular and adrenal androgens during prolonged physical exercise in man.

The evolution of the relationship between cortisol and testicular androgens was verified on two teams of respectively 10 and 9 male subjects (average age 34) running 100 km races in an average time of 14 hours. When compared to a control population of the same age, these trained athletes exhibited reduced testicular androgen levels (T and DHT) and increased adrenal androgen (delta 4) and cortisol levels with no significant alteration of LH. The period of recovery is characterized by rapid return to normal of the hormonal parameters whereas testosterone levels continue to increase in the following days. This hormonal picture, which reappears under certain pathological situations or when subjects are exposed to heavy stresses, seems to prove that the testicular androgens could be, both by their metabolic and psychic action, one of the limiting factors of physical aptitude to sustained effort.