Growth hormone and testosterone: anabolic effects on muscle

BACKGROUND: The loss of skeletal muscle mass that occurs with aging, chronic disease or acute injury is clinically important in the health of humans. The mechanisms relating to the synthesis and breakdown of skeletal muscle are now being intensely investigated. Current studies and possible mechanisms for skeletal muscle protein synthesis and degradation will be reviewed with a specific focus on growth hormone and testosterone. CONCLUSIONS: Investigation of the mechanisms of action of growth hormone and testosterone in skeletal muscle will likely lead to new therapies to prevent skeletal muscle loss and new awareness of the importance of skeletal muscle in health and disease.     

Differential anabolic effects of testosterone and amino acid feeding in older men

The interaction between testosterone and exogenous amino acids was studied in older men before and after 6 months of testosterone administration. Twelve healthy older male subjects were randomly assigned in double-blind fashion to receive either testosterone enanthate [T; n = 7; 68 +/- 3 (+/-SE) yr] or placebo (n = 5; 67 +/- 3 yr) for 6 months. Muscle protein kinetics were determined using stable isotope methodology, arterial-venous difference across leg muscle, and muscle biopsies. In addition, ubiquitin-proteasome activity was measured in muscle biopsies as an indicator of muscle protein breakdown. T improved fasting net protein balance, although it remained significantly negative. The improvement in net balance was due to a decrease in muscle protein breakdown, as protein synthesis was unchanged. Ubiquitin-proteasome activity was also decreased with T. Exogenous amino acids increased protein synthesis in both placebo and T groups, but to a lesser degree after 6 months of T treatment. These results indicate that prolonged T administration increases net protein balance in the fasted state, but no additive effect is demonstrated when combined with amino acid feedings. Taken together, however, these diverse stimulatory effects can increase lean body mass and muscle strength over time.     

The role of GH and IGF-I in mediating anabolic effects of testosterone on androgen-responsive muscle

Testosterone (T) supplementation increases skeletal muscle mass, circulating GH, IGF-I, and im IGF-I expression, but the role of GH and IGF-I in mediating T's effects on the skeletal muscle remains poorly understood. Here, we show that T administration increased body weight and the mass of the androgen-dependent levator ani muscle in hypophysectomized as well as castrated plus hypophysectomized adult male rats. T stimulated the proliferation of primary human skeletal muscle cells (hSKMCs) in vitro, an effect blocked by transfecting hSKMCs with small interference RNA targeting human IGF-I receptor (IGF-IR). In differentiation conditions, T promoted the fusion of hSKMCs into larger myotubes, an effect attenuated by small interference RNA targeting human IGF-IR. Notably, MKR mice, which express a dominant negative form of the IGF-IR in skeletal muscle fibers, treated with a GnRH antagonist (acyline) to suppress endogenous T, responded to T administration by an attenuated increase in the levator ani muscle mass. In conclusion, circulating GH and IGF-I are not essential for mediating T's effects on an androgen-responsive skeletal muscle. IGF-I signaling plays an important role in mediating T's effects on skeletal muscle progenitor cell growth and differentiation in vitro. However, IGF-IR signaling in skeletal muscle fibers does not appear to be obligatory for mediating the anabolic effects of T on the mass of androgen-responsive skeletal muscles in mice.     

Pharmacokinetic properties of testosterone propionate in normal men

The pharmacokinetic characteristics of testosterone propionate were studied in normal men after a single im dose of 25 mg testosterone propionate-19,19,19-d3. Plasma levels of testosterone propionate-19,19,19-d3, its active metabolite testosterone-19,19,19-d3, and endogenous testosterone were measured by gas chromatography-mass spectrometry. Testosterone propionate-19,19,19-d3 was gradually transferred from the im injection site to the systemic circulation. The plasma levels of testosterone propionate-19,19,19-d3 were maintained at 2-4 ng/ml between 3 and 36 h after administration. Plasma testosterone-19,19,19-d3 levels were maintained above the physiological testosterone level for 48 h, while plasma levels of endogenous testosterone changed little.     

Amelioratory effects of testosterone propionate supplement on behavioral, biochemical and morphological parameters in aged rats

Testosterone has been shown to affect motor behavior and nigrostriatal dopaminergic (NSDA) system in young and adult male rats. However, it is not known whether exogenous testosterone intervention to aged male rats can ameliorate age-related motor impairment. Thus, in the present study, the open field motor behavior and adhesive tape removal motor performance as well as the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) of NSDA system were examined in aged male rats following chronic subcutaneous injections of testosterone propionate (TP). Aged rats showed significantly reduced open field motor behavior and adhesive tape removal motor performance compared to adult rats. Chronic TP supplement significantly ameliorated the age-related motor deficits. The expression of TH and DAT of NSDA system was significantly enhanced in TP-treated aged rats revealed by RT-PCR, Western blot and immunohistochemistry analysis respectively. The results imply that chronic TP treatment may favorably improve the declined motor behavior and motor performance with aging. Testosterone propionate supplement that facilitated NSDA system may influence the maintenance of motor behavior and performance in aged rats.