The effects of exogenous testosterone (T) administration on muscle protein anabolism and lean body mass accrual are well established. The muscle protein kinetic mechanisms through which T administration improves anabolism are less appreciated. Fasted net muscle protein balance is improved in healthy males following a 5d treatment with an oral T analogue [1] or T injection [2]. Muscle protein synthesis (PS) improves with T in fasted muscle of healthy males [1, 2], in part by improving synthetic efficiency, where synthetic efficiency refers to the rate of PS relative to the availablilty of amino acid (AA) precursors. In the post-absorptive state, the essential AA precursors for PS at the whole body level are derived entirely from protein breakdown (PB). In certain tissues and organs, the precursors for PS can be derived from uptake of circulating AA. Improved synthetic efficiency of muscle protein in the post-absorptive state in response to T refers to an increase in the rate of PS relative to the rates of PB and inward AA transport [1, 2]. Greater anabolism is achieved when hyperaminoacidemia accompanies T administration through greater increases in inward AA transport, intracellular AA appearance, and subsequently PS [3]. Enhanced muscle protein synthetic efficiency has also been observed in a severely injured clinical population, as administering T for 2 weeks to severely burned patients improves the synthesis/breakdown ratio. However, unlike healthy adults, synthesis and breakdown are both dramatically upregulated in burn patients [4], thus the increase in protein synthetic efficiency secondary to T administration is due to a maintenance of the rate of PS and a reduction in the rate of PB [5]. As such, our work utilizing T for 5 days or longer demonstrates effects on muscle protein kinetics. Whether the effects of exogenous T on muscle protein kinetics occur acutely upon exposure is not known.

We sought to discern the effects of acute T administration on muscle protein kinetics. The investigation centered on the concept of a potential hormonal-induced change in protein kinetics. For example, muscle anabolism and inward AA transport were upregulated with acute insulin infusion [6]. Whether an analogous response was present with T is not known. Although the primary mechanism of T in skeletal muscle is genomic via the androgen receptor, Estrada and colleagues [7] demonstrated T can stimulate extracellular signal-related kinase 1 and 2, which are involved in cellular growth, within a minute in cultured myotubes. Furthermore, the G-coupled protein receptor GPRC6A, a widely expressed calcium and amino acid sensor, has been implicated in the non-genomic action of T [8]. This question may be relevant to populations who are not generally considered for clinical T treatment and are routinely exposed to acute catabolic stress. More specifically, T may be a viable option to conserve muscle mass and ultimately function in healthy poplutations exposed to extreme stress, such as military personnel, including light infantry and special operations forces, who can experience high energy expenditures, severe energy deficits, sleep deprivation, and environmental stress during trainings and combat operations. These exposures typically last ~ 3–60 days and elicit a marked hypogonadal state and catabolism of lean mass [9,10,11]. In this context, delineating the acute effects of T on skeletal muscle will help refine future efforts to minimize muscle loss in military personnel [12]. Therefore, the purpose of this study, which was conducted in 1995, was to detail the results of a 5 h (hr) T infusion on muscle protein turnover and AA transport in young males using stable isotope methodology and cross-limb modelling kinetics. We hypothesized that exposure to 5 h of T would confer anabolic effects on skeletal muscle. It is important to note that while we previously referred to the results of this study in a brief review [13], the data were never published. Therefore, the effects of acute exposure to T on muscle protein turnover are undetermined.