Exercise interrupts ongoing glucocorticoid-induced muscle atrophy and glutamine synthetase induction

2006 ◽  
Vol 263 (6) ◽  
pp. E1157-E1163
Author(s):  
M. T. Falduto ◽  
A. P. Young ◽  
R. C. Hickson
Keyword(s):  
Enzyme Activity ◽  
Glutamine Synthetase ◽  
Muscle Atrophy ◽  
Contractile Activity ◽  
Hormone Treatment ◽  
Quadriceps Muscle ◽  
Treadmill Running ◽  
Female Rats ◽  
Glucocorticoid Treatment ◽  
Fast Twitch

This study was undertaken to determine whether regular endurance exercise is a deterrent to a developing state of muscle atrophy from glucocorticoids and to evaluate whether the contractile activity antagonizes the hormonal actions on glutamine synthetase, alanine aminotransferase, and cytosolic aspartate aminotransferase (cAspAT). Adult female rats were administered cortisol acetate (CA, 100 mg/kg body wt) or an equal volume of the vehicle solution for up to 15 days. Exercise (treadmill running at 31 m/min, 10% grade, 90 min/day) was introduced after 4 days of CA treatment, at which time plantaris and quadriceps muscle mass had been reduced to 90% of control levels. Running for 11 consecutive days prevented 40 mg of the 90-mg loss and 227 mg of the 808-mg loss that were subsequently observed in plantaris and quadriceps muscles, respectively, in the sedentary animals. Glutamine synthetase mRNA and enzyme activity were elevated threefold by glucocorticoid treatment in the deep quadriceps (fast-twitch red) muscles after 4 days. Initiating exercise completely interfered with the further hormonal induction (to approximately 5-fold) of this enzyme and, after 11 consecutive days of the exercise regimen, glutamine synthetase mRNA and enzyme activity were 58 and 68% of values from CA-treated sedentary animals. In vehicle-treated groups, basal levels of glutamine synthetase expression were also diminished by exercise to approximately 40% of the values in sedentary controls. Hormone treatment did not alter either aminotransferase enzyme activity but reduced cAspAT mRNA in fast-twitch red muscles by 50%. Exercise abolished the glucocorticoid effect on cAspAT mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise interrupts ongoing glucocorticoid-induced muscle atrophy and glutamine synthetase induction

1992 ◽  
Vol 263 (6) ◽  
pp. E1157-E1163 ◽  
Author(s):  
M. T. Falduto ◽  
A. P. Young ◽  
R. C. Hickson
Keyword(s):  
Enzyme Activity ◽  
Glutamine Synthetase ◽  
Muscle Atrophy ◽  
Contractile Activity ◽  
Hormone Treatment ◽  
Quadriceps Muscle ◽  
Treadmill Running ◽  
Female Rats ◽  
Glucocorticoid Treatment ◽  
Fast Twitch

This study was undertaken to determine whether regular endurance exercise is a deterrent to a developing state of muscle atrophy from glucocorticoids and to evaluate whether the contractile activity antagonizes the hormonal actions on glutamine synthetase, alanine aminotransferase, and cytosolic aspartate aminotransferase (cAspAT). Adult female rats were administered cortisol acetate (CA, 100 mg/kg body wt) or an equal volume of the vehicle solution for up to 15 days. Exercise (treadmill running at 31 m/min, 10% grade, 90 min/day) was introduced after 4 days of CA treatment, at which time plantaris and quadriceps muscle mass had been reduced to 90% of control levels. Running for 11 consecutive days prevented 40 mg of the 90-mg loss and 227 mg of the 808-mg loss that were subsequently observed in plantaris and quadriceps muscles, respectively, in the sedentary animals. Glutamine synthetase mRNA and enzyme activity were elevated threefold by glucocorticoid treatment in the deep quadriceps (fast-twitch red) muscles after 4 days. Initiating exercise completely interfered with the further hormonal induction (to approximately 5-fold) of this enzyme and, after 11 consecutive days of the exercise regimen, glutamine synthetase mRNA and enzyme activity were 58 and 68% of values from CA-treated sedentary animals. In vehicle-treated groups, basal levels of glutamine synthetase expression were also diminished by exercise to approximately 40% of the values in sedentary controls. Hormone treatment did not alter either aminotransferase enzyme activity but reduced cAspAT mRNA in fast-twitch red muscles by 50%. Exercise abolished the glucocorticoid effect on cAspAT mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanyl-glutamine prevents muscle atrophy and glutamine synthetase induction by glucocorticoids

1996 ◽  
Vol 271 (5) ◽  
pp. R1165-R1172
Author(s):  
R. C. Hickson ◽  
L. E. Wegrzyn ◽  
D. F. Osborne ◽  
I. E. Karl
Keyword(s):  
Enzyme Activity ◽  
Glutamine Synthetase ◽  
Muscle Atrophy ◽  
Quadriceps Muscle ◽  
Muscle Fiber Types ◽  
Fiber Types ◽  
Glucocorticoid Treatment ◽  
Catabolic State ◽  
Total Body ◽  
Fast Twitch

The aims of this work were to establish whether glutamine infusion via alanyl-glutamine dipeptide provides effective therapy against muscle atrophy from glucorticoids and whether the glucocorticoid induction of glutamine synthetase (GS) is downregulated by dipeptide supplementation. Rats were given hydrocortisone 21-acetate or the dosing vehicle and were infused with alanine (AA) or alanyl-glutamine (AG) at the same concentrations and rates (1.15 mumol.min-1.100 g body wt-1, 0.75 ml/h) for 7 days. Compared with AA infusion in hormone-treated animals, AG infusion prevented total body and fast-twitch muscle mass losses by over 70%. Glucocorticoid treatment did not reduce muscle glutamine levels. Higher serum glutamine was found in the AG-infused (1.72 +/- 0.28 mumol/ml) compared with the AA-infused group (1.32 +/- 0.06 mumol/ml), but muscle glutamine concentrations were not elevated by AG infusion. Following glucocorticoid injections, GS enzyme activity was increased by two- to threefold in plantaris, fast-twitch white (superficial quadriceps), and fast-twitch red (deep quadriceps) muscle/fiber types of the AA group. Similarly, GS mRNA was elevated by 3.3- to 4.1-fold in these same muscles of hormone-treated, AA-infused rats. AG infusion diminished glucocorticoid effects on GS enzyme activity to 52-65% and on GS mRNA to 31-37% of the values with AA infusion. These results provide firsthand evidence of atrophy prevention from a catabolic state using glutamine in dipeptide form. Despite higher serum and muscle alanine levels with AA infusion than with AG infusion, alanine alone is not a sufficient stimulus to counteract muscle atrophy. The AG-induced muscle sparing is accompanied by diminished expression of a glucocorticoid-inducible gene in skeletal muscle. However, glutamine regulation of GS appears complex and may involve more regulators than muscle glutamine concentration alone.

Glutamine interferes with glucocorticoid-induced expression of glutamine synthetase in skeletal muscle

1996 ◽  
Vol 270 (5) ◽  
pp. E912-E917 ◽  
Author(s):  
R. C. Hickson ◽  
L. E. Wegrzyn ◽  
D. F. Osborne ◽  
I. E. Karl
Keyword(s):  
Skeletal Muscle ◽  
Enzyme Activity ◽  
Glutamine Synthetase ◽  
Hormone Treatment ◽  
Skeletal Muscle Atrophy ◽  
Fiber Types ◽  
Gene Encoding ◽  
Glucocorticoid Treatment ◽  
Amino Acid Infusion ◽  
Fast Twitch

Skeletal muscle atrophy from glucocorticoids is prevented by glutamine infusion. Because the gene-encoding glutamine synthetase (GS) is glucocorticoid inducible, it represented an appropriate model for resting whether glucocorticoids and glutamine exert opposing actions on the expression of specific genes related to atrophy in muscle tissue. Rats were administered hydrocortisone 21-acetate or the dosing vehicle (carboxymethyl cellulose) and were infused with saline (Sal) or glutamine (Gln, 240 mM, 0.75 ml/h) for 7 days. Hormone treatment did not significantly lower glutamine levels in fast-twitch white or red regions of the quadriceps. Despite higher serum glutamine concentrations with amino acid infusion [1.52 +/- 0.03 (Gln) vs. 1.20 +/- 0.04 (Sal) mumol/ml], muscle glutamine concentrations were not markedly increased in these fiber types. In saline-infused animals, glucocorticoid treatment produced 200-300% increases in plantaris, fast-twitch white, and fast-twitch red muscle GS enzyme activity and mRNA. Moreover, in all muscle types studied, glutamine infusion diminished glucocorticoid effects on GS enzyme activity to 131-159% and on GS mRNA to 110-200% of the values in saline-treated controls. These data demonstrate that glutamine infusion results in inhibiting GS expression, but the absence of changes in muscle glutamine concentration suggests the interplay of additional regulators of the GS gene.

Exercise inhibits glucocorticoid-induced glutamine synthetase expression in red skeletal muscles

1992 ◽  
Vol 262 (1) ◽  
pp. C214-C220 ◽  
Author(s):  
M. T. Falduto ◽  
A. P. Young ◽  
R. C. Hickson
Keyword(s):  
Enzyme Activity ◽  
Glutamine Synthetase ◽  
Contractile Activity ◽  
Treadmill Running ◽  
Fiber Types ◽  
Muscle Type ◽  
Endurance Running ◽  
Muscle Types ◽  
Slow Twitch ◽  
Fast Twitch

One purpose of this study was to determine whether the suppression of glucocorticoid-induced glutamine synthetase (GS) gene expression by exercise is localized to fiber types that are known to be primarily recruited during endurance running. A second purpose examined whether denervation, which is associated with a reduction in contractile activity, would upregulate GS expression. Exercise consisted of treadmill running at 31 m/min for 12-16 wk. Glucocorticoid treatment (100 mg/kg body wt hydrocortisone 21-acetate) was administered during the last 11 days of the exercise program. Basal GS expression was lowest (GS enzyme activity, 43 +/- 3 nmol.h-1.mg protein-1; GS mRNA, 1.0 arbitrary units) in the slow-twitch red soleus, a muscle type that is known to resist glucocorticoid-induced muscle wasting, intermediate (74 +/- 10 and 1.7 +/- 0.2) in fast-twitch red quadriceps, a muscle type susceptible to atrophy, and highest (106 +/- 16 and 5.4 +/- 1.3) in fast-twitch white quadriceps, a muscle type known to be most susceptible to atrophy. Hormone treatment increased GS enzyme activity and mRNA by two- to fourfold in all muscle types. Exercise diminished GS enzyme activity and mRNA in the fast-twitch red fibers to 35-70% of sedentary control values in both basal and glucocorticoid-stimulated muscles. The running also reduced GS enzyme activity in hormone-treated slow-twitch fibers but did not alter basal or glucocorticoid-induced GS expression in fast-twitch white fibers. These results indicate that glucocorticoids induce similar relative GS expression across all muscle types, but the low absolute levels of expression in slow-twitch muscles are not related to any atrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of glucocorticoids and endurance training on cytochrome oxidase expression in skeletal muscle

1994 ◽  
Vol 77 (4) ◽  
pp. 1685-1690 ◽  
Author(s):  
J. R. Marone ◽  
M. T. Falduto ◽  
D. A. Essig ◽  
R. C. Hickson
Keyword(s):  
Endurance Training ◽  
Exercise Program ◽  
Treadmill Running ◽  
Female Rats ◽  
Glucocorticoid Treatment ◽  
Subunit Mrna ◽  
Mrna Content ◽  
Muscle Groups ◽  
Coordinate Changes ◽  
Fast Twitch

This investigation was undertaken to evaluate whether the mitochondrial disfunction associated with glucocorticoid treatment is expressed at the level of cytochrome-c oxidase (COX) and whether endurance training attenuates this response. Adult female rats were administered cortisol acetate (100 mg/kg body wt) or an equal volume of the vehicle solution for 11 days. Endurance training was performed by treadmill running up to 28 m/min (with intervals at 50 m/min for 2 min every 15 min), for 90 min/day, 6 days/wk, for 8–10 wk. During hormone treatments, the training animals ran every day. Exercise prevented 43–55% of the hormone-induced atrophy in various fast-twitch muscles or muscle groups. Cortisol acetate treatment produced no significant effects on COX enzyme activities or subunit mRNA content in deep red or superficial white quadriceps or mixed plantaris muscles. The levels of COX were increased as a result of training by 70–110% in plantaris and red quadriceps muscles, but no changes were seen in white quadriceps muscles. Both nuclear-encoded (COX IV) and mitochondrial-encoded (COX III) mRNAs were increased approximately twofold by the exercise program in these same muscles. These data indicate that the impaired mitochondrial functioning associated with glucocorticoids is not observed at the COX step of electron transport. The prolonged endurance-training regimen appears to induce relatively parallel increases in COX enzyme activity and mRNA expression with coordinate changes in nuclear and mitochondrial mRNAs.

Glutamine synthetase induction by glucocorticoids is preserved in skeletal muscle of aged rats

1996 ◽  
Vol 271 (6) ◽  
pp. E1061-E1066 ◽  
Author(s):  
D. Meynial-Denis ◽  
M. Mignon ◽  
A. Miri ◽  
J. Imbert ◽  
E. Aurousseau ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glutamine Synthetase ◽  
Skeletal Muscles ◽  
Female Rats ◽  
Mrna Levels ◽  
Aged Rats ◽  
Adult Rats ◽  
Adult Age ◽  
Slow Twitch ◽  
Fast Twitch

Glutamine synthetase (GS) is a glucocorticoid-inducible enzyme that has a key role for glutamine synthesis in muscle. We hypothesized that the glucocorticoid induction of GS could be altered in aged rats, because alterations in the responsiveness of some genes to glucocorticoids were reported in aging. We compared the glucocorticoid-induced GS in fast-twitch and slow-twitch skeletal muscles (tibialis anterior and soleus, respectively) and heart from adult (age 6-8 mo) and aged (age 22 mo) female rats. All animals received dexamethasone (Dex) in their drinking water (0.77 +/- 0.10 and 0.80 +/- 0.08 mg/day per adult and aged rat, respectively) for 5 days. Dex caused an increase in both GS activity and GS mRNA in fast-twitch and slow-twitch skeletal muscles from adult and aged rats. In contrast, Dex increased GS activity in heart of adult rats, without any concomitant change in GS mRNA levels. Furthermore, Dex did not affect GS activity in aged heart. Thus the responsiveness of GS to an excess of glucocorticoids is preserved in skeletal muscle but not in heart from aged animals.

Glutamine prevents downregulation of myosin heavy chain synthesis and muscle atrophy from glucocorticoids

1995 ◽  
Vol 268 (4) ◽  
pp. E730-E734 ◽  
Author(s):  
R. C. Hickson ◽  
S. M. Czerwinski ◽  
L. E. Wegrzyn
Keyword(s):  
Protein Synthesis ◽  
Myosin Heavy Chain ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Heavy Chain ◽  
Total Protein ◽  
Female Rats ◽  
Glucocorticoid Treatment ◽  
Precursor Pool ◽  
Chain Synthesis

The aims of this study were to determine whether glutamine infusion prevents the decline in protein synthesis and muscle wasting associated with repeated glucocorticoid treatment. Hormone (cortisol acetate, 100 mg.kg body wt-1.day-1) and vehicle (carboxymethyl cellulose)-treated female rats were infused with either saline or glutamine (240 mM, 0.75 ml/h) for a 7-day period. Glutamine infusion attenuated the decline of plantaris muscle glutamine concentration (3.0 +/- 0.2 vs. 2.3 +/- 0.2 mumol/g) and prevented > 70% of the total muscle mass losses due to the glucocorticoid injections. Fractional synthesis rates of myosin heavy chain (MHC) and total protein were determined after constant [3H]leucine infusion from the leucyl-tRNA precursor pool, which was similar in all groups (range 4.8 +/- 0.5 to 6.3 +/- 0.4 disintegrations.min-1.pmol-1). MHC synthesis rates (%/day) in plantaris muscles were reduced to approximately 40% of controls (4.2/9.4). Although glutamine had no effect on MHC synthesis in vehicle-treated animals (10.1/9.4), it prevented 50% (7.6/4.2) of the hormone-induced decline in MHC synthesis rates. The same results were obtained with total protein synthesis measurements. Changes in muscle mass did not appear related to estimates of protein breakdown. In conclusion, these data show that glutamine infusion is effective therapy in counteracting glucocorticoid-induced muscle atrophy. Atrophy attenuation appears related to maintaining muscle glutamine levels, which in turn may limit the glucocorticoid-mediated downregulation of MHC synthesis.

Testosterone fails to prevent skeletal muscle atrophy from glucocorticoids

1987 ◽  
Vol 63 (1) ◽  
pp. 328-334 ◽  
Author(s):  
J. A. Capaccio ◽  
T. T. Kurowski ◽  
S. M. Czerwinski ◽  
R. T. Chatterton ◽  
R. C. Hickson
Keyword(s):  
Triamcinolone Acetonide ◽  
Muscle Atrophy ◽  
Specific Binding ◽  
Muscle Growth ◽  
Deae Cellulose ◽  
Treated Group ◽  
Female Rats ◽  
Skeletal Muscle Atrophy ◽  
Glucocorticoid Treatment ◽  
Group A

This study was undertaken to determine whether testosterone can stimulate muscle growth as well as counteract the muscle wasting caused by excess glucocorticoids. Female rats were divided into four groups: a vehicle (1% carboxymethycellulose)-treated group, a testosterone acetate (Te)-treated group, a cortisol acetate (Co)-treated group, and a Te + Co group. Animals were injected with the steroids (Te, 40 mg/kg body wt; Co, 20 mg/kg body wt) subcutaneously for 12 consecutive days. Absolute gastrocnemius muscle weights were 8% heavier after testosterone treatment, (P less than 0.05), 20% lighter after glucocorticoid treatment, and 18% lighter after both treatments than those of vehicle-treated animals. However, total body weight loss was less in the Te + Co group than in the group receiving just Co. Specific binding of [3H]triamcinolone acetonide, a synthetic glucocorticoid, in femtomoles per milligram gastrocnemius cytosol protein, was similar between the vehicle-treated (52.9 +/- 4.7) and Te-treated (48.9 +/- 3.6) groups. Specific cytosol binding was also depleted to the same extent (to 11–12 fmol/mg protein) by either the Co or Te + Co injections. There was minimal competition by testosterone for glucocorticoid binding; however, most of the displacement was observed in the corticosteroid binder IB form of the activated triamcinolone acetonide-receptor complex on DEAE-cellulose chromatography. We conclude that Te was ineffective in preventing muscle atrophy caused by Co treatment despite its ability to induce muscle growth. The binding specificity studies lead to the conclusion that most of the testosterone and cortisol functioning were occurring primarily through separate receptor systems.

Skeletal muscle cytochrome c and myoglobin, endurance, and frequency of training

1981 ◽  
Vol 51 (3) ◽  
pp. 746-749 ◽  
Author(s):  
R. C. Hickson
Keyword(s):  
Skeletal Muscle ◽  
Cytochrome C ◽  
Vastus Lateralis ◽  
Training Group ◽  
Treadmill Running ◽  
Female Rats ◽  
Time To Exhaustion ◽  
Training Frequency ◽  
Muscle Types ◽  
Fast Twitch

This study was undertaken to evaluate the effects of various training frequencies on performance capacity, the mitochondrial marker cytochrome c, and myoglobin, which is responsible for storage and transport of O2, in the three types of skeletal muscle. Female rats were trained by treadmill running up to 120 min/day, either 2, 4, or 6 days/wk for 14 wk. As a result of training, exercise time to exhaustion was increased in proportion to the number of training sessions per week. Cytochrome c concentration increased (range 20–90%) as a linear function of the number of exercises per week in the fast-twitch red vastus lateralis (FTR), the slow-twitch soleus (STR), and the mixed plantaris muscles. However, the concentration of cytochrome c in fast-twitch white vastus lateralis (FTW) muscles increased to approximately the same extent (40–50%) in all training groups. The increases in myoglobin concentration (13–45%) with training were significantly related to frequency in FTR muscle but not in STR muscle. Myoglobin levels in FTW muscle remained unchanged, regardless of training group. These results provide evidence that the capacity to perform endurance exercise and the mitochondrial content of the red skeletal muscle types are directly affected by training frequency.

Energy metabolism in contracting rat skeletal muscle: adaptation to exercise training

1987 ◽  
Vol 253 (2) ◽  
pp. C316-C322 ◽  
Author(s):  
S. H. Constable ◽  
R. J. Favier ◽  
J. A. McLane ◽  
R. D. Fell ◽  
M. Chen ◽  
...  
Keyword(s):  
Contractile Activity ◽  
Treadmill Running ◽  
Muscle Adaptation ◽  
Rat Skeletal Muscle ◽  
Plantaris Muscle ◽  
Hindlimb Muscles ◽  
P Concentration ◽  
Steady State Levels ◽  
Fast Twitch ◽  
Adaptation To Exercise

Rats were trained by means of a program of treadmill running. Hindlimb muscles were stimulated to contract in anesthetized rats. Measurements were made on the plantaris and the deep, predominantly fast-twitch red portion of the gastrocnemius. The concentration of ATP plus phosphocreatine (approximately P) decreased less and stabilized at a higher level, whereas inorganic phosphate (Pi) and AMP concentrations increased less and attained lower steady-state levels in trained than in untrained muscles at the same work rate. Similarly, when muscles were stimulated to contract in the perfused rat hindquarter preparation, phosphocreatine (PC) concentration decreased less in trained plantaris muscle during contractile activity that resulted in the same rate of oxygen uptake by trained and untrained muscles. In both preparations, glycogen concentration decreased less and lactate increased less in the trained muscle. From the changes that occurred in the PC-to-creatine ratio during contractile activity and from ATP concentration, it could be estimated that free ADP concentration increased less than one-half as much in trained as in untrained muscles. We conclude that, as a consequence of the adaptive increase in muscle mitochondria, approximately P concentration is higher and Pi, ADP, and AMP concentrations are lower in muscles of exercise-trained compared with untrained rats during the same contractile activity.

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