madman
Super Moderator
Abstract
We previously demonstrated that improved net muscle protein balance, via enhanced protein synthetic efficiency, occurs 5 days after testosterone (T) administration. Whether the effects of T on muscle protein kinetics occur immediately upon exposure is not known. We investigated the effects of acute T exposure on leg muscle protein kinetics and selected amino acid (AA) transport using the arteriovenous balance model, and direct calculations of mixed-muscle protein fractional synthesis (FSR) and breakdown (FBR) rates. Four healthy men were studied over a 5 h period with and without T (infusion rate, 0.25 mg·min− 1 ). Muscle protein FSR, FBR, and net protein balance (direct measures and model derived) were not affected by T, despite a significant increases in arterial (p = 0.009) and venous (p = 0.064) free T area under the curve during T infusion. T infusion had minimal effects on AA transport kinetics, affecting only the outward transport and total intracellular rate of appearance of leucine. These data indicate that exposing skeletal muscle to T does not confer immediate effects on AA kinetics or muscle anabolism. There remains an uncertainty as to the earliest discernable effects of T on skeletal muscle protein kinetics after initial administration.
Conclusion
The most important aspect highlighted by this research, is that there exists a gap in our experimental knowledge of T effects on muscle protein kinetics. We now know that there are no acute T effects; however, we also know that the earliest demonstrated effects, due to a lack of experimental data, are 5 days after administration [1, 2]. Thus, we have a knowledge gap in terms of the initiation of protein kinetic effects that spans from the time point of administration until 5 days post-administration. This gap has never been of clinical significance, since T administration is normally given for extended periods of time to correct hypogonadal states, or more recently, during hypocaloric states in obese populations [24–26]. Even when utilized in severe burn injury [5], intensive care treatment of this populations entails administration for 1 month or longer [27]. However, the efficacy of T administration in healthy populations exposed to severe catabolic stress for short durations highlights a need to close this knowledge gap. In particular, special operations forces combat training results in a hypogonadal state [11, 28, 29], a loss of lean mass [10, 11, 30], and decreased performance outcomes due to a convergence of many different physiological and environmental stressors [29, 31–34]. Thus, the ability to discern the short-term anabolic potential of T may be of substantial benefit to certain military populations whose occupational demands often include exposure to extreme catabolic stress. The current study indicates that within hours of administration, there are no remarkable effects of T on protein kinetics. What remains is the elucidation and magnitude of T effects on protein kinetics between the time of administration and the 5 day period that has been reported [1–3].
We previously demonstrated that improved net muscle protein balance, via enhanced protein synthetic efficiency, occurs 5 days after testosterone (T) administration. Whether the effects of T on muscle protein kinetics occur immediately upon exposure is not known. We investigated the effects of acute T exposure on leg muscle protein kinetics and selected amino acid (AA) transport using the arteriovenous balance model, and direct calculations of mixed-muscle protein fractional synthesis (FSR) and breakdown (FBR) rates. Four healthy men were studied over a 5 h period with and without T (infusion rate, 0.25 mg·min− 1 ). Muscle protein FSR, FBR, and net protein balance (direct measures and model derived) were not affected by T, despite a significant increases in arterial (p = 0.009) and venous (p = 0.064) free T area under the curve during T infusion. T infusion had minimal effects on AA transport kinetics, affecting only the outward transport and total intracellular rate of appearance of leucine. These data indicate that exposing skeletal muscle to T does not confer immediate effects on AA kinetics or muscle anabolism. There remains an uncertainty as to the earliest discernable effects of T on skeletal muscle protein kinetics after initial administration.
Conclusion
The most important aspect highlighted by this research, is that there exists a gap in our experimental knowledge of T effects on muscle protein kinetics. We now know that there are no acute T effects; however, we also know that the earliest demonstrated effects, due to a lack of experimental data, are 5 days after administration [1, 2]. Thus, we have a knowledge gap in terms of the initiation of protein kinetic effects that spans from the time point of administration until 5 days post-administration. This gap has never been of clinical significance, since T administration is normally given for extended periods of time to correct hypogonadal states, or more recently, during hypocaloric states in obese populations [24–26]. Even when utilized in severe burn injury [5], intensive care treatment of this populations entails administration for 1 month or longer [27]. However, the efficacy of T administration in healthy populations exposed to severe catabolic stress for short durations highlights a need to close this knowledge gap. In particular, special operations forces combat training results in a hypogonadal state [11, 28, 29], a loss of lean mass [10, 11, 30], and decreased performance outcomes due to a convergence of many different physiological and environmental stressors [29, 31–34]. Thus, the ability to discern the short-term anabolic potential of T may be of substantial benefit to certain military populations whose occupational demands often include exposure to extreme catabolic stress. The current study indicates that within hours of administration, there are no remarkable effects of T on protein kinetics. What remains is the elucidation and magnitude of T effects on protein kinetics between the time of administration and the 5 day period that has been reported [1–3].
