Effect of testosterone on muscle mass and muscle protein synthesis

1989 ◽  
Vol 66 (1) ◽  
pp. 498-503 ◽  
Author(s):  
R. C. Griggs ◽  
W. Kingston ◽  
R. F. Jozefowicz ◽  
B. E. Herr ◽  
G. Forbes ◽  
...  

We have studied the effect of a pharmacological dose of testosterone enanthate (3 mg.kg-1.wk-1 for 12 wk) on muscle mass and total-body potassium and on whole-body and muscle protein synthesis in normal male subjects. Muscle mass estimated by creatinine excretion increased in all nine subjects (20% mean increase, P less than 0.02); total body potassium mass estimated by 40K counting increased in all subjects (12% mean increase, P less than 0.0001). In four subjects, a primed continuous infusion protocol with L-[1–13C]leucine was used to determine whole-body leucine flux and oxidation. Whole-body protein synthesis was estimated from nonoxidative flux. Muscle protein synthesis rate was determined by measuring [13C]leucine incorporation into muscle samples obtained by needle biopsy. Testosterone increased muscle protein synthesis in all subjects (27% mean increase, P less than 0.05). Leucine oxidation decreased slightly (17% mean decrease, P less than 0.01), but whole-body protein synthesis did not change significantly. Muscle morphometry showed no significant increase in muscle fiber diameter. These studies suggest that testosterone increases muscle mass by increasing muscle protein synthesis.

1998 ◽  
Vol 275 (4) ◽  
pp. E577-E583 ◽  
Author(s):  
Kevin E. Yarasheski ◽  
Jeffrey J. Zachwieja ◽  
Jennifer Gischler ◽  
Jan Crowley ◽  
Mary M. Horgan ◽  
...  

Muscle protein wasting occurs in human immunodeficiency virus (HIV)-infected individuals and is often the initial indication of acquired immunodeficiency syndrome (AIDS). Little is known about the alterations in muscle protein metabolism that occur with HIV infection. Nine subjects with AIDS wasting (CD4 < 200/mm3), chronic stable opportunistic infections (OI), and ≥10% weight loss, fourteen HIV-infected men and one woman (CD4 > 200/mm3) without wasting or OI (asymptomatic), and six HIV-seronegative lean men (control) received a constant intravenous infusion of [1-13C]leucine (Leu) and [2-15N]glutamine (Gln). Plasma Leu and Gln rate of appearance (Ra), whole body Leu turnover, disposal and oxidation rates, and [13C]Leu incorporation rate into mixed muscle protein were assessed. Total body muscle mass/fat-free mass was greater in controls (53%) than in AIDS wasting (43%; P = 0.04). Fasting whole body proteolysis and synthesis rates were increased above control in the HIV+ asymptomatic group and in the AIDS-wasting group ( P = 0.009). Whole body Leu oxidation rate was greater in the HIV+ asymptomatic group than in the control and AIDS-wasting groups ( P < 0.05). Fasting mixed muscle protein synthesis rate was increased in the asymptomatic subjects (0.048%/h; P = 0.01) but was similar in AIDS-wasting and control subjects (0.035 vs. 0.037%/h). Plasma Gln Rawas increased in AIDS-wasting subjects but was similar in control and HIV+ asymptomatic subjects ( P < 0.001). These findings suggest that AIDS wasting results from 1) a preferential reduction in muscle protein, 2) a failure to sustain an elevated rate of mixed muscle protein synthesis while whole body protein synthesis is increased, and 3) a significant increase in Gln release into the circulation, probably from muscle. Several interesting explanations for the increased Gln Rain AIDS wasting exist.


1992 ◽  
Vol 262 (3) ◽  
pp. E261-E267 ◽  
Author(s):  
K. E. Yarasheski ◽  
J. A. Campbell ◽  
K. Smith ◽  
M. J. Rennie ◽  
J. O. Holloszy ◽  
...  

The purpose of this study was to determine whether growth hormone (GH) administration enhances the muscle anabolism associated with heavy-resistance exercise. Sixteen men (21-34 yr) were assigned randomly to a resistance training plus GH group (n = 7) or to a resistance training plus placebo group (n = 9). For 12 wk, both groups trained all major muscle groups in an identical fashion while receiving 40 micrograms recombinant human GH.kg-1.day-1 or placebo. Fat-free mass (FFM) and total body water increased (P less than 0.05) in both groups but more (P less than 0.01) in the GH recipients. Whole body protein synthesis rate increased more (P less than 0.03), and whole body protein balance was greater (P = 0.01) in the GH-treated group, but quadriceps muscle protein synthesis rate, torso and limb circumferences, and muscle strength did not increase more in the GH-treated group. In the young men studied, resistance exercise with or without GH resulted in similar increments in muscle size, strength, and muscle protein synthesis, indicating that 1) the larger increase in FFM with GH treatment was probably due to an increase in lean tissue other than skeletal muscle and 2) resistance training supplemented with GH did not further enhance muscle anabolism and function.


1997 ◽  
Vol 273 (5) ◽  
pp. E898-E902 ◽  
Author(s):  
Odile Mansoor ◽  
Marc Cayol ◽  
Pierre Gachon ◽  
Yves Boirie ◽  
Pierre Schoeffler ◽  
...  

The effect of trauma on protein metabolism was investigated in the whole body, muscle, and liver in severely head-injured patients presenting an acute inflammatory response by comparison to fed control subjects receiving a similar diet. Nonoxidative leucine disposal (an index of whole body protein synthesis) and muscle, albumin, and fibrinogen synthesis were determined by means of a primed, continuous infusion ofl-[1-13C]leucine. Nonoxidative leucine disposal increased by 28% in the patients ( P < 0.02). Fractional muscle protein synthesis rate decreased by 50% ( P < 0.01) after injury. Fractional and absolute fribrinogen synthesis rates were multiplied by two and nine, respectively, after injury ( P< 0.001). Albumin levels were lower in patients (25.2 ± 1.2 g/l, means ± SE) than in controls (33.7 ± 1.2 g/l, P < 0.001). However, fractional albumin synthesis rates were increased by 60% in patients (11.4 ± 1.0%/day) compared with controls (7.3 ± 0.4%/day, P < 0.01). Therefore, 1) head trauma induces opposite and large changes of protein synthesis in muscle and acute-phase hepatic proteins, probably mediated by cytokines, glucocorticoids, and other stress hormones, and 2) in these patients, hypoalbuminemia is not due to a depressed albumin synthesis.


1988 ◽  
Vol 254 (2) ◽  
pp. E208-E213 ◽  
Author(s):  
K. S. Nair ◽  
D. Halliday ◽  
R. C. Griggs

Fractional mixed skeletal muscle protein synthesis (FMPS) was estimated in 10 postabsorptive healthy men by determining the increment in the abundance of [13C]-leucine in quadriceps muscle protein during an intravenous infusion of L-[1-13C]leucine. FMPS in our subjects was 0.046 +/- 0.003%/h. Whole-body muscle protein synthesis (MPS) was calculated based on the estimation of muscle mass from creatinine excretion and compared with whole-body protein synthesis (WBPS) calculated from the nonoxidative portion of leucine flux. A significant correlation (r2 = 0.73, P less than 0.05) was found between MPS (44.7 +/- 3.4 mg.kg-1.h-1) and WBPS (167.8 +/- 8.5 mg.kg-1.h-1). The contribution of MPS to WBPS was 27 +/- 1%, which is comparable to the reports in other species. Morphometric analyses of adjacent muscle samples in eight subjects demonstrated that the biopsy specimens consisted of 86.5 +/- 2% muscular as opposed to other tissues. Because fiber type composition varies between biopsies, we examined the relationship between proportions of each fiber type and FMPS. Variation in the composition of biopsies and in fiber-type proportion did not affect the estimation of muscle protein synthesis rate. We conclude that stable isotope techniques using serial needle biopsies permit the direct measurement of FMPS in humans and that this estimation is correlated with an indirect estimation of WBPS.


2011 ◽  
Vol 106 (11) ◽  
pp. 1683-1690 ◽  
Author(s):  
Stéphane Walrand ◽  
Aude Zangarelli ◽  
Christelle Guillet ◽  
Jérôme Salles ◽  
Karine Soulier ◽  
...  

Sarcopenia is defined as age-related loss of muscle mass and strength. Energy restriction (ER) delays fibre loss by limiting the accumulated deleterious effects of reactive oxygen species on muscle. However, insufficient protein intake during ER might affect muscle mass and function. We hypothesised that ingestion of fast-digested proteins such as whey protein (WP) improves muscle protein synthesis and muscle strength in aged ER rats. The effect of WP or casein (CAS, slow protein) on muscle mass, protein synthesis and strength was evaluated in 21-month-old rats fed for 5 months either ad libitum (AL) or a 40 % protein and energy-restricted (PER) or 40 % AL-isonitrogenous ER diet. The nitrogen balance was reduced in PER-CAS rats only ( − 48 % v. AL-CAS). WP stimulated muscle protein synthesis rates compared with CAS in all groups (+21,+37 and +34 % in AL, PER and ER conditions, respectively). Muscle strength was higher in ER rats than in AL rats (+23 and +12 % for WP or CAS, respectively). Muscle performance tended to be greater in ER rats fed WP than in ER-CAS rats (P < 0·09). In conclusion, we observed that long-term ER combined with maintained protein intake had a beneficial impact on muscle protein synthesis rate and function during ageing.


2007 ◽  
Vol 293 (3) ◽  
pp. E833-E842 ◽  
Author(s):  
René Koopman ◽  
Milou Beelen ◽  
Trent Stellingwerff ◽  
Bart Pennings ◽  
Wim H. M. Saris ◽  
...  

The present study was designed to assess the impact of coingestion of various amounts of carbohydrate combined with an ample amount of protein intake on postexercise muscle protein synthesis rates. Ten healthy, fit men (20 ± 0.3 yr) were randomly assigned to three crossover experiments. After 60 min of resistance exercise, subjects consumed 0.3 g·kg−1·h−1 protein hydrolysate with 0, 0.15, or 0.6 g·kg−1·h−1 carbohydrate during a 6-h recovery period (PRO, PRO + LCHO, and PRO + HCHO, respectively). Primed, continuous infusions with l-[ ring-13C6]phenylalanine, l-[ ring-2H2]tyrosine, and [6,6-2H2]glucose were applied, and blood and muscle samples were collected to assess whole body protein turnover and glucose kinetics as well as protein fractional synthesis rate (FSR) in the vastus lateralis muscle over 6 h of postexercise recovery. Plasma insulin responses were significantly greater in PRO + HCHO compared with PRO + LCHO and PRO (18.4 ± 2.9 vs. 3.7 ± 0.5 and 1.5 ± 0.2 U·6 h−1·l−1, respectively, P < 0.001). Plasma glucose rate of appearance (Ra) and disappearance (Rd) increased over time in PRO + HCHO and PRO + LCHO, but not in PRO. Plasma glucose Ra and Rd were substantially greater in PRO + HCHO vs. both PRO and PRO + LCHO ( P < 0.01). Whole body protein breakdown, synthesis, and oxidation rates, as well as whole body protein balance, did not differ between experiments. Mixed muscle protein FSR did not differ between treatments and averaged 0.10 ± 0.01, 0.10 ± 0.01, and 0.11 ± 0.01%/h in the PRO, PRO + LCHO, and PRO + HCHO experiments, respectively. In conclusion, coingestion of carbohydrate during recovery does not further stimulate postexercise muscle protein synthesis when ample protein is ingested.


1995 ◽  
Vol 268 (1) ◽  
pp. E67-E74 ◽  
Author(s):  
Z. Rifai ◽  
S. Welle ◽  
R. T. Moxley ◽  
M. Lorenson ◽  
R. C. Griggs

Prednisone improves strength in Duchenne dystrophy and changes the natural history of the disease. We studied the in vivo effects of prednisone (0.75 mg.kg-1.day-1) on muscle and whole body protein metabolism in six patients with Duchenne dystrophy and three patients with Becker dystrophy. Patients were admitted to the Clinical Research Center for study and consumed a constant flesh-free diet. Strength was measured by manual and quantitative muscle testing. Fractional muscle protein breakdown was estimated by the ratio of 3-methylhistidine to creatinine excretion determined in three consecutive 24-h urine collections. Whole body protein kinetics were studied in the postabsorptive state using a primed continuous infusion of L-[1-13C]leucine. Fractional muscle protein synthesis was determined from tracer incorporation into noncollagen muscle protein obtained by needle biopsy. After 6-8 wk of prednisone treatment, average muscle strength increased by 15% (P < 0.04), and 24-h creatinine excretion (an index of muscle mass) increased by 21% (P = 0.002). 3-Methylhistidine excretion decreased by 10%, but the change was not statistically significant. The ratio of 3-methylhistidine to creatinine excretion decreased by 26% (P < 0.04). Fractional muscle protein synthesis and whole body protein synthesis and breakdown did not change significantly. We conclude that the beneficial effect of prednisone on strength in Duchenne dystrophy appears to be associated with an increase in muscle mass, which may be mediated by inhibition of muscle proteolysis rather than stimulation of muscle protein synthesis.


2002 ◽  
Vol 282 (3) ◽  
pp. E551-E556 ◽  
Author(s):  
T. A. Trappe ◽  
F. White ◽  
C. P. Lambert ◽  
D. Cesar ◽  
M. Hellerstein ◽  
...  

We examined the effect of two commonly consumed over-the-counter analgesics, ibuprofen and acetaminophen, on muscle protein synthesis and soreness after high-intensity eccentric resistance exercise. Twenty-four males (25 ± 3 yr, 180 ± 6 cm, 81 ± 6 kg, and 17 ± 8% body fat) were assigned to one of three groups that received either the maximal over-the-counter dose of ibuprofen (IBU; 1,200 mg/day), acetaminophen (ACET; 4,000 mg/day), or a placebo (PLA) after 10–14 sets of 10 eccentric repetitions at 120% of concentric one-repetition maximum with the knee extensors. Postexercise (24 h) skeletal muscle fractional synthesis rate (FSR) was increased 76 ± 19% ( P < 0.05) in PLA (0.058 ± 0.012%/h) and was unchanged ( P > 0.05) in IBU (35 ± 21%; 0.021 ± 0.014%/h) and ACET (22 ± 23%; 0.010 ± 0.019%/h). Neither drug had any influence on whole body protein breakdown, as measured by rate of phenylalanine appearance, on serum creatine kinase, or on rating of perceived muscle soreness compared with PLA. These results suggest that over-the-counter doses of both ibuprofen and acetaminophen suppress the protein synthesis response in skeletal muscle after eccentric resistance exercise. Thus these two analgesics may work through a common mechanism to influence protein metabolism in skeletal muscle.


2015 ◽  
Vol 173 (1) ◽  
pp. R25-R34 ◽  
Author(s):  
Jorn Trommelen ◽  
Bart B L Groen ◽  
Henrike M Hamer ◽  
Lisette C P G M de Groot ◽  
Luc J C van Loon

BackgroundThough it is well appreciated that insulin plays an important role in the regulation of muscle protein metabolism, there is much discrepancy in the literature on the capacity of exogenous insulin administration to increase muscle protein synthesis ratesin vivoin humans.ObjectiveTo assess whether exogenous insulin administration increases muscle protein synthesis rates in young and older adults.DesignA systematic review of clinical trials was performed and the presence or absence of an increase in muscle protein synthesis rate was reported for each individual study arm. In a stepwise manner, multiple models were constructed that excluded study arms based on the following conditions: model 1, concurrent hyperaminoacidemia; model 2, insulin-induced hypoaminoacidemia; model 3, supraphysiological insulin concentrations; and model 4, older, more insulin resistant, subjects.ConclusionsFrom the presented data in the current systematic review, we conclude that: i) exogenous insulin and amino acid administration effectively increase muscle protein synthesis, but this effect is attributed to the hyperaminoacidemia; ii) exogenous insulin administered systemically induces hypoaminoacidemia which obviates any insulin-stimulatory effect on muscle protein synthesis; iii) exogenous insulin resulting in supraphysiological insulin levels exceeding 50 000 pmol/l may effectively augment muscle protein synthesis; iv) exogenous insulin may have a diminished effect on muscle protein synthesis in older adults due to age-related anabolic resistance; and v) exogenous insulin administered systemically does not increase muscle protein synthesis in healthy, young adults.


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