metribolone and Hypertrophy

The changes in the number of androgen receptors in rat gastrocnemius muscle following muscle contraction caused by electrical stimulation were investigated. The gastrocnemius muscle of one leg, which was selected at random for each rat, was stimulated with needle type electrodes, e.g. for 2 s at 10 V and 100 Hz, with 5-s intervals. The contralateral leg was left unstimulated as a control. One set consisted of ten such stimuli, followed by 5-min rest. Three sets every 2 days caused a statistically significant increase in muscle mass, the increase being about 2.5% after the 3rd day of stimulation, 4.4% after the 5th day, 5.9% after the 13th day and 8.3% after the 27th day compared with each control muscle (P < 0.001 in each case). The protein content also increased but the water content did not change. Stimulation over 4 weeks induced an increase in the area of the cross-section of the muscle fibres to about 30% more than that of the control muscles, though the total muscle fibre numbers were slightly, but significantly, reduced. Electromechanical properties supported the development of the muscle by stimulation, because the maximal isometric tetanic force and peak twitch force markedly increased in the stimulated muscle. The androgen receptors in the muscle cytosol fraction were determined by means of a binding assay involving [3H]methyltrienolone, which is an analogue of testosterone, the number having rapidly increased in the stimulated leg, when compared with that in the control leg, by about 25% after the 3rd day. The increase then slowed down, reaching a plateau after the 5th-day of stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Analysis of Variance; Animals; Dihydrotestosterone; Electric Stimulation; Electrophysiology; Hypertrophy; Male; Metribolone; Muscle Contraction; Muscles; Rats; Rats, Sprague-Dawley; Receptors, Androgen; Testosterone; Time Factors

This study was undertaken to evaluate whether the increased androgen cytosol binding is an early or later event in the sequence of skeletal muscle hypertrophy induced by surgical overload. Following removal of the synergistic gastrocnemius and soleus muscles, plantaris muscle weights of overloaded hypophysectomized made rats were heavier than those in the control by 29% at 2 days, 41% at 7 days, 38% at 14 days, and 47% at 35 days. Androgen cytosol receptor binding capacities (femtomoles per milligram protein), determined using a synthetic androgen, [3H]methyltrienolone (R1881), were higher than observed in muscles of controls at all points of muscle enlargement. At high concentrations of labeled ligand, Scatchard analyses became nonlinear and were resolved using a two-component binding model. Receptor capacity of the higher affinity "androgenic component" for methyltrienolone binding in plantaris muscles was lower at 2 days but 60-80% higher at 7, 14, and 35 days in the hypertrophied group than in the control group. The lower affinity "glucocorticoid component" was higher in the overloaded group at all points following surgery. Several glucocorticoids and estradiol-17 beta competed equally with androgens for methyltrienolone binding. However, when cytosols were incubated with triamcinolone acetonide to block methyltrienolone binding to glucocorticoid receptors, the androgenic component was highly specific for androgens. These results show that total [3H]methyltrienolone cytosol concentrations increased in parallel with the muscle hypertrophy, yet the individual components of methyltrienolone binding attained greater concentrations in overloaded muscles by an apparently different sequence of events.

Topics: Androgens; Animals; Cytosol; Estrenes; Hypertrophy; Hypophysectomy; Male; Metribolone; Muscles; Organ Size; Rats; Rats, Inbred Strains; Receptors, Androgen; Receptors, Steroid; Testosterone Congeners; Time Factors

Normal, castrated, and hypophysectomized male rats underwent compensatory hypertrophy of plantaris muscles following surgical removal of their synergistic gastrocnemius muscles. The increases in muscle wet weights above control values, determined when the muscles were in stable-state hypertrophy, were as follows: normal 50%, castrated 50%, and hypophysectomized 32%. There were marked differences in concentration of serum androgens between surgical groups, yet no increases in testosterone or 5 alpha-dihydrotestosterone were observed as a result of hypertrophy. The amount of testosterone binding to serum proteins (approx 94%) was reduced only in hypophysectomized animals that underwent muscle growth. Cytosol androgen receptor specific binding (fmol/mg protein), measured using saturating concentrations of [3H]methyltrienolone (R1881) at 4 degrees C for 20 h for exchange with endogenous steroid, was significantly increased in hypertrophied muscles of normal, (1.77 +/- 0.17 vs 1.16 +/- 0.21), castrated (2.27 +/- 0.20 vs 1.46 +/- 0.03) and hypophysectomized (6.23 +/- 0.56 vs 3.64 +/- 0.30) animals. Receptor dissociation constants (Kd) were approx 10(-10) M in all groups and were not altered by the hypertrophy. These findings show that a major adaptation to skeletal muscle enlargement is an augmentation of cytosol [3H]methyltrienolone receptor binding capacity. This effect occurs in a normal or androgen deficient state.

Topics: Androgens; Animals; Castration; Cytosol; Estrenes; Hypertrophy; Hypophysectomy; Male; Metribolone; Muscles; Rats; Rats, Inbred Strains; Receptors, Androgen; Receptors, Steroid; Testosterone