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Short-Term Oxandrolone Administration Stimulates Net Muscle Protein Synthesis in Young Men
http://jcem.endojournals.org/cgi/co...33c6e08a627fd3d
ATHLETES have long used anabolic agents for improving lean muscle mass and strength. However, clinicians have only recently recognized the benefits of anabolic agents for patients with trauma- and disease-related muscle wasting. Recently, several clinical studies demonstrated the positive benefits of testosterone (T) administration to various patient populations. In particular, hypogonadal men benefit from T replacement therapy via enhanced skeletal muscle mass (1, 2, 3), increased bone density (2), and increased protein synthesis (1). Likewise, elderly men receiving T replacement therapy have increased lean body mass (4), strength (5), and protein synthesis (5) along with decreased bone resorption (4). Moreover, changes in body composition, including a loss in lean body mass, are highly correlated with androgen levels in hypogonadal men with the acquired immunodeficiency syndrome (AIDS) wasting myopathy (6).
We recently showed that T enanthate (TE), administered im to healthy young men, increased net protein synthesis and reutilization of intracellular amino acids in skeletal muscle (7). In addition, several other studies have found T administration to increase muscle protein synthesis (1, 5, 8), although these studies failed to measure protein breakdown. One of the major limitations of previous studies of fractional synthetic rate (FSR) is that no estimation of protein breakdown could be made simultaneously. Consequently, the traditional approach to the study of muscle protein kinetics (i.e. FSR) provided no information on the net balance between synthesis and breakdown. Therefore, our laboratory developed a new method for measuring fractional protein breakdown that is independent of the arterio-venous (A-V) model (9).
Although natural androgens such as T clearly stimulate muscle protein synthesis, they also possess androgenic or virilizing effects. Often this limits the clinician’s use of these androgens to specific patient populations such as hypogonadal men. However, efforts have been made to find alternative anabolic agents that can be used in women and children suffering from muscle-wasting diseases or trauma. Oxandrolone [Oxandrin (OX) Bio-Technology General, Iselin, NJ], a synthetic analog of T, is an oral anabolic steroid currently used as an adjunctive therapy to promote weight gain in patients after surgery, chronic infections, and severe trauma. OX improved weight gain in patients experiencing AIDS-wasting myopathy (10) as well as in convalescing burn patients (30–50% total body surface area burns) (11). In addition, OX is used by clinicians to treat children with growth disorders such as Turner’s syndrome and constitutional delay of growth and puberty (12, 13). A recent pilot study in boys with Duchenne muscular dystrophy found that OX, given at a dose of 0.1 mg/kg·day, improved muscle strength over a 3-month period (14). Given that OX is administered orally, as opposed to im as with TE, its ease of administration makes it attractive to clinicians and patients alike. Further, OX is purported to have a much greater anabolic potential than T, with fewer of the androgenic effects. However, no studies have demonstrated whether OX, similar to TE, promotes the stimulation of protein synthesis in skeletal muscle.
Hence, we investigated whether OX, a purported anabolic agent, improves net muscle protein synthesis and transport of amino acids in fasted young men. The present study was designed to mimic the 5-day TE study in normal males previously discussed (7). We sought to evaluate the short term (5-day) effects a moderate dose (15 mg/day) of OX on the incorporation of amino acids into muscle proteins using an established protein kinetic model (15, 16). We further examined the effect of OX on the messenger ribonucleic acid (mRNA) concentrations of skeletal muscle insulin-like growth factor I (IGF-I) and androgen receptors (AR).
In summary, this study demonstrates that OX, administered once a day at a moderate dose (15 mg/day), promotes net muscle protein synthesis. Moreover, these data suggest that OX induced an increase in AR expression as a mechanism for the increase in net muscle protein synthesis.
Short-Term Oxandrolone Administration Stimulates Net Muscle Protein Synthesis in Young Men
http://jcem.endojournals.org/cgi/co...33c6e08a627fd3d
ATHLETES have long used anabolic agents for improving lean muscle mass and strength. However, clinicians have only recently recognized the benefits of anabolic agents for patients with trauma- and disease-related muscle wasting. Recently, several clinical studies demonstrated the positive benefits of testosterone (T) administration to various patient populations. In particular, hypogonadal men benefit from T replacement therapy via enhanced skeletal muscle mass (1, 2, 3), increased bone density (2), and increased protein synthesis (1). Likewise, elderly men receiving T replacement therapy have increased lean body mass (4), strength (5), and protein synthesis (5) along with decreased bone resorption (4). Moreover, changes in body composition, including a loss in lean body mass, are highly correlated with androgen levels in hypogonadal men with the acquired immunodeficiency syndrome (AIDS) wasting myopathy (6).
We recently showed that T enanthate (TE), administered im to healthy young men, increased net protein synthesis and reutilization of intracellular amino acids in skeletal muscle (7). In addition, several other studies have found T administration to increase muscle protein synthesis (1, 5, 8), although these studies failed to measure protein breakdown. One of the major limitations of previous studies of fractional synthetic rate (FSR) is that no estimation of protein breakdown could be made simultaneously. Consequently, the traditional approach to the study of muscle protein kinetics (i.e. FSR) provided no information on the net balance between synthesis and breakdown. Therefore, our laboratory developed a new method for measuring fractional protein breakdown that is independent of the arterio-venous (A-V) model (9).
Although natural androgens such as T clearly stimulate muscle protein synthesis, they also possess androgenic or virilizing effects. Often this limits the clinician’s use of these androgens to specific patient populations such as hypogonadal men. However, efforts have been made to find alternative anabolic agents that can be used in women and children suffering from muscle-wasting diseases or trauma. Oxandrolone [Oxandrin (OX) Bio-Technology General, Iselin, NJ], a synthetic analog of T, is an oral anabolic steroid currently used as an adjunctive therapy to promote weight gain in patients after surgery, chronic infections, and severe trauma. OX improved weight gain in patients experiencing AIDS-wasting myopathy (10) as well as in convalescing burn patients (30–50% total body surface area burns) (11). In addition, OX is used by clinicians to treat children with growth disorders such as Turner’s syndrome and constitutional delay of growth and puberty (12, 13). A recent pilot study in boys with Duchenne muscular dystrophy found that OX, given at a dose of 0.1 mg/kg·day, improved muscle strength over a 3-month period (14). Given that OX is administered orally, as opposed to im as with TE, its ease of administration makes it attractive to clinicians and patients alike. Further, OX is purported to have a much greater anabolic potential than T, with fewer of the androgenic effects. However, no studies have demonstrated whether OX, similar to TE, promotes the stimulation of protein synthesis in skeletal muscle.
Hence, we investigated whether OX, a purported anabolic agent, improves net muscle protein synthesis and transport of amino acids in fasted young men. The present study was designed to mimic the 5-day TE study in normal males previously discussed (7). We sought to evaluate the short term (5-day) effects a moderate dose (15 mg/day) of OX on the incorporation of amino acids into muscle proteins using an established protein kinetic model (15, 16). We further examined the effect of OX on the messenger ribonucleic acid (mRNA) concentrations of skeletal muscle insulin-like growth factor I (IGF-I) and androgen receptors (AR).
In summary, this study demonstrates that OX, administered once a day at a moderate dose (15 mg/day), promotes net muscle protein synthesis. Moreover, these data suggest that OX induced an increase in AR expression as a mechanism for the increase in net muscle protein synthesis.