Effects of the anabolic steroid stanozolol on growth and protein metabolism in the rat

1987 ◽  
Vol 114 (3) ◽  
pp. 373-381 ◽  
Author(s):  
P. C. Bates ◽  
L. F. Chew ◽  
D. J. Millward
Keyword(s):  
Protein Synthesis ◽  
Anabolic Steroid ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Muscle Growth ◽  
Female Rats ◽  
Male Rats ◽  
Anabolic Action ◽  
Rna Concentration

ABSTRACT The effects of the anabolic steroid stanozolol on whole body and muscle growth and protein metabolism in the rat have been examined. No responses could be found in normal well-fed male rats. Female rats responded to 1 mg/kg per day with an increased body and skeletal muscle growth rate and an increase in muscle protein synthesis. The anabolic action on muscle protein synthesis was due to increased RNA concentration with no change in the rate of protein synthesis per unit RNA (KRNA). Investigation of any anticatabolic effects of stanozolol treatment in male rats deprived of food for 24 h indicated no response of protein balance and turnover. However, rats treated with catabolic doses of corticosterone (50 mg/kg per day) did respond to stanozolol with decreased muscle growth inhibition due to better-maintained muscle protein synthesis. The latter response was due to a reversal of the corticosterone-induced reduction of KRNA, but with no effect on RNA concentration. Thus there appear to be at least two effects of stanozolol; an anabolic action evident only in female rats, involving increased muscle RNA concentrations, and an anticatabolic action involving inhibition of the corticosterone-induced fall in muscle RNA activity. In both cases, stanozolol influenced muscle protein synthesis with no evident effects on protein degradation. J. Endocr. (1987) 114, 373–381

scholarly journals Stimulation of muscle growth by clenbuterol: lack of effect on muscle protein biosynthesis

1986 ◽  
Vol 56 (1) ◽  
pp. 249-258 ◽  
Author(s):  
Peter J. Reeds ◽  
Susan M. Hay ◽  
Patricia M. Dorwood ◽  
Robert M. Palmer
Keyword(s):  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Protein Biosynthesis ◽  
Muscle Growth ◽  
Inhibitory Effect ◽  
Male Rats ◽  
Promoting Effect ◽  
Physiological Mechanisms ◽  
Direct Inhibitory Effect

1. Young rats were offered to appetite a semi-synthetic diet either alone or containing the β2-selective agonist clenbuterol (4-amino-α[t-butylamino) methyl]-3, 5-dichlorobenzyl alcohol).3. Male rats (starting weight 53 g) received clenbuterol at a daily oral dose of 200 pg/kg body-weight per d. Animals were slaughtered after 0, 4, 8, 11, 18, 21 and 25 d of treatment. At 4, 11, 21 and 25 d muscle protein synthesis was measured by the method of Garlick et al. (1980). Although clenbuterol increased the rate of protein and RNA accretion in gastrocnemius and soleus muscles, protein synthesis was not increased.4. The results suggested that the drug had a rapid, perhaps direct, inhibitory effect on protein degradation. It is concluded that the growth-promoting effect of clenbuterol may be specific to muscle and that the drug may act in a novel manner which circumvents the physiological mechanisms responsible for the control of muscle growth.

scholarly journals Exercise, Protein Metabolism, and Muscle Growth

2001 ◽  
Vol 11 (1) ◽  
pp. 109-132 ◽  
Author(s):  
Kevin D. Tipton ◽  
Robert R. Wolfe
Keyword(s):  
Protein Synthesis ◽  
Protein Metabolism ◽  
Muscle Hypertrophy ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Muscle Growth ◽  
Protein Breakdown ◽  
Muscle Protein Breakdown ◽  
Amino Acid Availability ◽  
Muscle Protein Metabolism

Exercise has a profound effect on muscle growth, which can occur only if muscle protein synthesis exceeds muscle protein breakdown; there must be a positive muscle protein balance. Resistance exercise improves muscle protein balance, but, in the absence of food intake, the balance remains negative (i.e., catabolic). The response of muscle protein metabolism to a resistance exercise bout lasts for 24-48 hours; thus, the interaction between protein metabolism and any meals consumed in this period will determine the impact of the diet on muscle hypertrophy. Amino acid availability is an important regulator of muscle protein metabolism. The interaction of postexercise metabolic processes and increased amino acid availability maximizes the stimulation of muscle protein synthesis and results in even greater muscle anabolism than when dietary amino acids are not present. Hormones, especially insulin and testosterone, have important roles as regulators of muscle protein synthesis and muscle hypertrophy. Following exercise, insulin has only a permissive role on muscle protein synthesis, but it appears to inhibit the increase in muscle protein breakdown. Ingestion of only small amounts of amino acids, combined with carbohydrates, can transiently increase muscle protein anabolism, but it has yet to be determined if these transient responses translate into an appreciable increase in muscle mass over a prolonged training period.

scholarly journals Proteasome- and Calpain-Mediated Proteolysis, but Not Autophagy, Is Required for Leucine-Induced Protein Synthesis in C2C12 Myotubes

Physiologia ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 22-33
Author(s):  
Shelby C. Osburn ◽  
Christopher G. Vann ◽  
David D. Church ◽  
Arny A. Ferrando ◽  
Michael D. Roberts
Keyword(s):  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Muscle Growth ◽  
Proteasome Inhibition ◽  
Coupled Processes ◽  
C2c12 Myotubes ◽  
Calpain Inhibitor ◽  
Tightly Coupled

Muscle protein synthesis and proteolysis are tightly coupled processes. Given that muscle growth is promoted by increases in net protein balance, it stands to reason that bolstering protein synthesis through amino acids while reducing or inhibiting proteolysis could be a synergistic strategy in enhancing anabolism. However, there is contradictory evidence suggesting that the proper functioning of proteolytic systems in muscle is required for homeostasis. To add clarity to this issue, we sought to determine if inhibiting different proteolytic systems in C2C12 myotubes in conjunction with acute and chronic leucine treatments affected markers of anabolism. In Experiment 1, myotubes underwent 1-h, 6-h, and 24-h treatments with serum and leucine-free DMEM containing the following compounds (n = 6 wells per treatment): (i) DMSO vehicle (CTL), (ii) 2 mM leucine + vehicle (Leu-only), (iii) 2 mM leucine + 40 μM MG132 (20S proteasome inhibitor) (Leu + MG132), (iv) 2 mM leucine + 50 μM calpeptin (calpain inhibitor) (Leu + CALP), and (v) 2 mM leucine + 1 μM 3-methyladenine (autophagy inhibitor) (Leu + 3MA). Protein synthesis levels significantly increased (p < 0.05) in the Leu-only and Leu + 3MA 6-h treatments compared to CTL, and levels were significantly lower in Leu + MG132 and Leu + CALP versus Leu-only and CTL. With 24-h treatments, total protein yield was significantly lower in Leu + MG132 cells versus other treatments. Additionally, the intracellular essential amino acid (EAA) pool was significantly greater in 24-h Leu + MG132 treatments versus other treatments. In a follow-up experiment, myotubes were treated for 48 h with CTL, Leu-only, and Leu + MG132 for morphological assessments. Results indicated Leu + MG132 yielded significantly smaller myotubes compared to CTL and Leu-only. Our data are limited in scope due to the utilization of select proteolysis inhibitors. However, this is the first evidence to suggest proteasome and calpain inhibition with MG132 and CALP, respectively, abrogate leucine-induced protein synthesis in myotubes. Additionally, longer-term Leu + MG132 treatments translated to an atrophy phenotype. Whether or not proteasome inhibition in vivo reduces leucine- or EAA-induced anabolism remains to be determined.

scholarly journals The influence of restraint and infusion on rates of muscle protein synthesis in the rat. Effect of altered respiratory function

1988 ◽  
Vol 251 (2) ◽  
pp. 577-580 ◽  
Author(s):  
V R Preedy ◽  
P J Garlick
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Respiratory Acidosis ◽  
Male Rats ◽  
Gas Measurements ◽  
Nutrient Administration ◽  
Fasted Rats ◽  
Infusion Period

1. Male rats (110-140 g body wt.) were restrained by a standard laboratory technique, by wrapping in a linen towel, and subjected to a constant intravenous infusion of saline (0.15 M-NaCl) for periods of 1 or 6 h. Fractional rates of protein synthesis (ks, %/day) were estimated at the start and at the end of the infusion period, by injection of a large concentration of [3H]phenylalanine. 2. In fed and overnight-fasted rats, restraint and infusion of saline for 1 and 6 h decreased ks in skeletal muscle by 15-20% and 30-35% respectively. Plasma glucose, insulin, glucagon and corticosterone concentrations in restrained and infused rats were not characteristic of immobilization stress. 3. Restrained rats responded to nutrient administration; ks in skeletal muscle increased by 35-40% after infusion of a mixture of amino acids and glucose for 1 or 6 h, as compared with saline-infused rats. 4. Restraint and infusion for 1 or 6 h did not overtly decrease ks and kRNA (protein synthesis per unit of RNA) in hypoxaemia-sensitive tissues, such as heart and liver. Restraint and infusion in an open cage, or in a cloth of open weave, did not decrease ks in muscle after 1 h. Blood gas measurements showed that rats restrained in a linen cloth were hypercapnic and acidotic compared with rats in an open cage. 5. It was concluded that respiratory acidosis, rather than hypoxia, resulting from restraint in a linen cloth decreases muscle protein synthesis.

scholarly journals Effects of acute oral feeding on protein metabolism and muscle protein synthesis in individuals with cancer

Nutrition ◽  
2019 ◽  
Vol 67-68 ◽  
pp. 110531 ◽  
Author(s):  
Barbara S. van der Meij ◽  
Lynette M. De Groot ◽  
Nicolaas E.P. Deutz ◽  
Mariëlle P.K.J. Engelen
Keyword(s):  
Protein Synthesis ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Oral Feeding

scholarly journals Glucocorticoid effects on insulin- and IGF-I-regulated muscle protein metabolism during aging

1998 ◽  
Vol 156 (1) ◽  
pp. 83-89 ◽  
Author(s):  
D Dardevet ◽  
C Sornet ◽  
I Savary ◽  
E Debras ◽  
P Patureau-Mirand ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Muscle Atrophy ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Recovery Period ◽  
Adult Rats ◽  
Igf I ◽  
Muscle Protein Metabolism ◽  
Old Rats

This study was performed to assess the effect of glucocorticoids (dexamethasone) on insulin- and IGF-I-regulated muscle protein metabolism in adult and old rats. Muscle atrophy occurred more rapidly in old rats, and recovery of muscle mass was impaired when compared with adults. Muscle wasting resulted mainly from increased protein breakdown in adult rat but from depressed protein synthesis in the aged animal. Glucocorticoid treatment significantly decreased the stimulatory effect of insulin and IGF-I on muscle protein synthesis in adult rats by 25.9 and 58.1% respectively. In old rats, this effect was even greater, being 49.3 and 100% respectively. With regard to muscle proteolysis, glucocorticoids blunted the anti-proteolytic action of insulin and IGF-I in both age groups. During the recovery period, adult rats reversed the glucocorticoid-induced resistance of muscle protein metabolism within 3 days, at which time old rats still exhibited the decrease in insulin-regulated proteolysis. In conclusion, the higher sensitivity of old rat muscle to glucocorticoids may in part result from the greater modification of the effects of insulin and IGF-I on muscle protein metabolism. These responses to glucocorticoids in old rats may be associated with the emergence of muscle atrophy with advancing age.

Availability of eIF4E regulates skeletal muscle protein synthesis during recovery from exercise

1998 ◽  
Vol 274 (2) ◽  
pp. C406-C414 ◽  
Author(s):  
T. A. Gautsch ◽  
J. C. Anthony ◽  
S. R. Kimball ◽  
G. L. Paul ◽  
D. K. Layman ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Plasma Concentrations ◽  
Male Rats ◽  
Skeletal Muscle Protein ◽  
Fourfold Increase ◽  
Skeletal Muscle Protein Synthesis ◽  
Translational Inhibitor

We examined the association of the mRNA cap binding protein eIF4E with the translational inhibitor 4E-BP1 in the acute modulation of skeletal muscle protein synthesis during recovery from exercise. Fasting male rats were run on a treadmill for 2 h at 26 m/min and were realimented immediately after exercise with either saline, a carbohydrate-only meal, or a nutritionally complete meal (54.5% carbohydrate, 14% protein, and 31.5% fat). Exercised animals and nonexercised controls were studied 1 h postexercise. Muscle protein synthesis decreased 26% after exercise and was associated with a fourfold increase in the amount of eIF4E present in the inactive eIF4E ⋅ 4E-BP1 complex and a concomitant 71% decrease in the association of eIF4E with eIF4G. Refeeding the complete meal, but not the carbohydrate meal, increased muscle protein synthesis equal to controls, despite similar plasma concentrations of insulin. Additionally, eIF4E ⋅ 4E-BP1 association was inversely related and eIF4E ⋅ eIF4G association was positively correlated to muscle protein synthesis. This study demonstrates that recovery of muscle protein synthesis after exercise is related to the availability of eIF4E for 48S ribosomal complex formation, and postexercise meal composition influences recovery via modulation of translation initiation.

Attenuated responses of muscle protein synthesis to fasting and insulin in adult female rats

1992 ◽  
Vol 262 (1) ◽  
pp. E1-E5 ◽  
Author(s):  
A. G. Baillie ◽  
P. J. Garlick
Keyword(s):  
Protein Synthesis ◽  
Adult Female ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Fiber Type ◽  
Female Rats ◽  
Adult Rats ◽  
Fractional Rate ◽  
The Individual

One-year-old adult female rats were fasted for 12 or 36 h followed by a 30-min infusion of insulin. The responses of the fractional rate of protein synthesis (Ks) in the individual muscles (measured in vivo) to fasting were small and mostly nonsignificant. After 12 h of fasting, only the epitrochlearis muscle (ET) showed a significant decrease in Ks, and, even after 36 h of fasting, a significant decrease in Ks was seen in only ET, extensor digitorum longus, and tensor fasciae latae (TFL). After the 36-h fast, infusion of insulin restored the fed Ks in all muscles except TFL. The fiber-type composition of the individual muscles appeared to influence the muscles' responsiveness to the fasting, since the highly glycolytic TFL was the most sensitive (particularly after 36 h of fasting), whereas the highly oxidative adductor longus and soleus muscles were unaffected by either fasting or insulin. In a second experiment, refeeding of fasted adult rats also had little effect on Ks, consistent with the low sensitivity to fasting shown by the first experiment. The parallel results in the two experiments confirmed that the low responsiveness to fasting and insulin infusion in these adult rats was not a result of failure to absorb in “fed” animals or insufficient levels of insulin during insulin infusions. In contrast, a third experiment showed that muscle protein synthesis in the gastrocnemius muscle from young adult (5-mo-old) female rats was significantly reduced after only 12 h of fasting.

scholarly journals Protein metabolism in the tumour-bearing mouse. Rates of protein synthesis in host tissues and in an Ehrlich ascites tumour at different stages in tumour growth

1989 ◽  
Vol 264 (3) ◽  
pp. 713-719 ◽  
Author(s):  
M N Lopes ◽  
P Black ◽  
A J Ashford ◽  
V M Pain
Keyword(s):  
Protein Synthesis ◽  
Food Intake ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Liver Protein ◽  
Humoral Factors ◽  
Ascites Tumour ◽  
Ehrlich Ascites ◽  
Ehrlich Ascites Tumour

We have investigated the time course of the changes in protein metabolism in skeletal muscle and liver in mice during the progression of growth of an Ehrlich ascites tumour. The rate of protein synthesis in muscle begins to fall very rapidly, and the decrease is clearly established by the time the tumour first becomes visible at 4 days after implantation of the cells. Liver protein synthesis increases substantially, and protein breakdown in muscle increases, but the onset of both these changes occurs later than the fall in muscle protein synthesis. A decrease in food intake in these animals occurs very rapidly after introduction of the cells. The fractional rate of protein synthesis in the tumour cells falls from 73%/day at 5 days to 26%/day at 12 days after injection, but on an absolute basis the rate of protein synthesis in the tumour at 5 days of growth is very small compared with that in muscle and liver. These results are consistent with the notion that the initial effects on muscle protein synthesis and food intake are brought about by humoral factors rather than as direct consequences of the metabolic demands of the growing tumour.

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