Evidence for a Non-Genomic Action of Testosterone in Skeletal Muscle Which may Improve Athletic Performance: Implications for the Female Athlete.

This review will focus on the proposed second mode of testosterone action (now termed non-genomic) that appears to occur independently of the traditional transcriptional mechanism in mammalian skeletal muscle cells which may enhance skeletal muscle contractile properties. This mechanism of testosterone action differs from the traditional pathway, originating at the cell membrane, having a rapid onset of action, requiring second messengers to execute its effects and is insensitive to inhibitors of traditional androgen receptor action, transcription and protein synthesis. Importantly, unlike the traditional action of testosterone in skeletal muscle, this non-genomic pathway is shown to have a direct acute effect on calcium-dependent components important for the contractile process. The changes within the contractile apparatus may enhance the ability of the muscle to produce explosive power during athletic performance. Rapid increases in Inositol triphosphate mass and calcium release from the sarcoplasmic reticulum have been reported in rodent skeletal muscle cells, and a rapid androgen (dihydrotestosterone)-induced increase in peak force production has been recorded in intact rodent skeletal muscle fibre bundles while showing increases in the activity of the Ras/MAP/ERK mediated pathway. Because the non-genomic action of testosterone is enhanced during increases in exposure to testosterone and is acute in its action, implications for athletic performance are likely greater in females than males due to natural fluctuations in circulating testosterone levels during the female menstrual cycle, reproductive pathology, and changes induced by hormonal contraceptive methods. Research should be undertaken in humans to confirm a pathway for non-genomic testosterone action in human skeletal muscle. Specifically, relationships between testosterone fluctuations and physiological changes within skeletal muscle cells and whole muscle exercise performance need to be examined. Key pointsNon-genomic calcium mediated events activated by testosterone have been identified in skeletal muscle cells.The non-genomic action originates at the cell membrane, is rapid in onset and is directed by second messengers' calcium and IP3.A possible action of non-genomic testosterone may be the initiation of a more efficient contraction through the mobilisation of calcium from the SR resulting in greater force production or velocity of contraction in fast twitch fibres.Physiologically, females with menstrual disorders that cause hyperandrogenism may have a performance advantage in events that require great force or power production.

Effect of a single and repeated dose of caffeine on antigen-stimulated human natural killer cell CD69 expression after high-intensity intermittent exercise.

Several studies investigating the effect of caffeine on immune function following exercise have used one large bolus dose of caffeine. However, this does not model typical caffeine consumption. Therefore, the purpose of this study was to investigate whether small repeated doses of caffeine ingested throughout the day would elicit a similar response as one large bolus dose ingested 1 h prior to exercise on antigen-stimulated NK cell CD69 expression following strenuous intermittent exercise. In a randomized cross-over design, 15 healthy males completed six 15 min blocks of intermittent running consisting of maximal sprinting interspersed with less intense running and walking. Participants had ingested either 0 (PLA), 2 mg kg(-1) body mass (BM) caffeine on three separate occasions during the day (3 × CAF) or one dose of 6 (1 × CAF) mg kg(-1) BM caffeine, 1 h before exercise. At 1-h post-exercise, the number of antigen-stimulated CD3(-)CD56(+) cells expressing CD69 was lower on 1 × CAF compared with PLA [P < 0.05; PLA: 42.0 (34.0) × 10(6) cells L(-1), 1 × CAF: 26.2 (25.0) × 10(6) cells L(-1)], with values on 1 × CAF at this time point remaining close to pre-supplement. 1 × CAF tended to attenuate the exercise-induced increase in geometric mean fluorescence intensity of CD69 expression on antigen-stimulated CD3(-)CD56(+) cells 1-h post-exercise [P = 0.055; PLA: 141 (28)%, 1 × CAF: 119 (20)%]. These findings suggest that although one large bolus dose of caffeine attenuated the exercise-induced increase in antigen-stimulated NK cell CD69 expression 1 h following strenuous intermittent exercise, this attenuation at no point fell below pre-supplement values and caffeine does not appear to depress NK cell CD69 expression.

Effect of a high and low dose of caffeine on antigen-stimulated activation of human natural killer cells after prolonged cycling.

This study investigated the effect of a high and low dose of caffeine on antigen-stimulated natural killer (NK) cell (CD3- CD56+) activation after prolonged, strenuous cycling, as assessed by the early-activation molecule CD69. In a randomized crossover design, 12 healthy male endurance-trained cyclists cycled for 90 min at 70% VO2peak 60 min after ingesting either 0 (PLA), 2 (2CAF), or 6 (6CAF) mg/kg body mass of caffeine. Whole blood was stimulated with Pediacel (5 in 1) vaccine. A high dose of caffeine (6CAF) increased the number of CD3-CD56+ cells in the circulation immediately postexercise compared with PLA (p < .05). For both 2CAF and 6CAF, the geometric mean fluorescence intensity (GMFI) of CD69+ expression on unstimulated CD3-CD56+ cells was significantly higher than with PLA (both p < .05). When cells were stimulated with antigen, the GMFI of CD69 expression remained significantly higher with 2CAF than with PLA 1 hr postexercise (p < .05). Although not achieving statistical significance, 6CAF also followed a similar trend when stimulated (p = .09). There were no differences in GMFI of CD69 expression between 2CAF and 6CAF. These results suggest that a high (6 mg/kg) dose of caffeine was associated with the recruitment of NK cells into the circulation and that both a high and low (2 mg/kg) dose of caffeine increased unstimulated and antigen-stimulated NK-cell activation 1 hr after high-intensity exercise. Furthermore, there does not appear to be a dose-dependent effect of caffeine on NK-cell activation 1 hr after prolonged intensive cycling.