Pressure-time product, work rate, and endurance during resistive breathing in humans

We examined the effect of increasing work rate, without a corresponding increase in the pressure-time product, on energy cost and inspiratory muscle endurance (Tlim) in five normal subjects during inspiratory resistive breathing. Tidal volume, mean inspiratory mouth pressure, duty cycle, and hence the pressure-time product were kept constant, whereas work rate was varied by changing the frequency of breathing. There was a linear decrease in Tlim of -2.1 +/- 0.5 s.J-1.min-1 (r = 0.87 +/- 0.06) with increasing work rate. The data satisfied a model of energy balance during fatiguing runs (Monod and Scherrer. Ergonomics 8: 329-337, 1965) and were consistent with the hypothesis that the rate of energy supply, or respiratory muscle blood flow, is fixed when the pressure-time product is constant. Our results indicate that during inspiratory resistive breathing against fatiguing loads, work rate determines endurance independently of the pressure-time product. On the basis of the model, our results lead to estimates of respiratory muscle blood flow and available energy stores under the conditions of our experiment.     

A simple model to link hemodynamics, fatigue and endurance in static work

This paper combines assumptions on blood flow changes during static work, on fatigue resulting from a shortage of chemical fuel, and on energy supply and demand considerations, to construct a systems model for endurance time in the maintenance of isometric muscle tension. All these quantitative assumptions are based on published experimental findings. The model is applied to published data on isometric endurance and a fit yielding R2 = 0.98 obtained on a composite data set.     

Model of oxygen transport and metabolism predicts effect of hyperoxia on canine muscle oxygen uptake dynamics.

Previous studies have shown that increased oxygen delivery, via increased convection or arterial oxygen content, does not speed the dynamics of oxygen uptake, Vo(2m), in dog muscle electrically stimulated at a submaximal metabolic rate. However, the dynamics of transport and metabolic processes that occur within working muscle in situ is typically unavailable in this experimental setting. To investigate factors affecting Vo(2m) dynamics at contraction onset, we combined dynamic experimental data across working muscle with a mechanistic model of oxygen transport and metabolism in muscle. The model is based on dynamic mass balances for O(2), ATP, and PCr. Model equations account for changes in cellular ATPase, oxidative phosphorylation, and creatine kinase fluxes in skeletal muscle during exercise, and cellular respiration depends on [ADP] and [O(2)]. Model simulations were conducted at different levels of arterial oxygen content and blood flow to quantify the effects of convection and diffusion of oxygen on the regulation of cellular respiration during step transitions from rest to isometric contraction in dog gastrocnemius muscle. Simulations of arteriovenous O(2) differences and (.)Vo(2m) dynamics were successfully compared with experimental data (Grassi B, Gladden LB, Samaja M, Stary CM, Hogan MC. J Appl Physiol 85: 1394-1403, 1998; and Grassi B, Gladden LB, Stary CM, Wagner PD, Hogan MC. J Appl Physiol 85: 1404-1412, 1998), thus demonstrating the validity of the model, as well as its predictive capability. The main findings of this study are: 1) the estimated dynamic response of oxygen utilization at contraction onset in muscle is faster than that of oxygen uptake; and 2) hyperoxia does not accelerate the dynamics of diffusion and consequently muscle oxygen uptake at contraction onset due to the hyperoxia-induced increase in oxygen stores. These in silico derived results cannot be obtained from experimental observations alone.     

Adipose triglyceride lipase plays a key role in the supply of the working muscle with fatty acids

FAs are mobilized from triglyceride (TG) stores during exercise to supply the working muscle with energy. Mice deficient for adipose triglyceride lipase (ATGL-ko) exhibit defective lipolysis and accumulate TG in adipose tissue and muscle, suggesting that ATGL deficiency affects energy availability and substrate utilization in working muscle. In this study, we investigated the effect of moderate treadmill exercise on blood energy metabolites and liver glycogen stores in mice lacking ATGL. Because ATGL-ko mice exhibit massive accumulation of TG in the heart and cardiomyopathy, we also investigated a mouse model lacking ATGL in all tissues except cardiac muscle (ATGL-ko/CM). In contrast to ATGL-ko mice, these mice did not accumulate TG in the heart and had normal life expectancy. Exercise experiments revealed that ATGL-ko and ATGL-ko/CM mice are unable to increase circulating FA levels during exercise. The reduced availability of FA for energy conversion led to rapid depletion of liver glycogen stores and hypoglycemia. Together, our studies suggest that ATGL-ko mice cannot adjust circulating FA levels to the increased energy requirements of the working muscle, resulting in an increased use of carbohydrates for energy conversion. Thus, ATGL activity is required for proper energy supply of the skeletal muscle during exercise.     

On facilitated oxygen diffusion in muscle tissues.

The role of myoglobin in facilitated diffusion of oxygen in muscle in examined in a tissue model that utilizes a central supplying capillary and a tissue cylinder concentric with the central capillary, and that includes the nonlinear characteristics of the oxygen-hemoglobin dissociation reaction. In contrast to previous work, this model exhibits the effect of blood flow and a realistic, though ideal, tissue-capillary geometry. Solutions of the model equations are obtained by a singular-perturbation technique, and numerical results are discussed for model parameters of physiologic interest. In contrast to the findings of Murray, Rubinow, Taylor, and others, fractional order perturbation terms obtained for the "boundary-layer" regions near the supplying capillaries are quite significant in the overall interpretation of the modeling results. Some closed solutions are found for special cases, and these are contrasted with the full singular-perturbation solution. Interpretations are given for parameters of physiologic interest.     

Resolving Shifting Patterns of Muscle Energy Use in Swimming Fish

Muscle metabolism dominates the energy costs of locomotion. Although in vivo measures of muscle strain, activity and force can indicate mechanical function, similar muscle-level measures of energy use are challenging to obtain. Without this information locomotor systems are essentially a black box in terms of the distribution of metabolic energy. Although in situ measurements of muscle metabolism are not practical in multiple muscles, the rate of blood flow to skeletal muscle tissue can be used as a proxy for aerobic metabolism, allowing the cost of particular muscle functions to be estimated. Axial, undulatory swimming is one of the most common modes of vertebrate locomotion. In fish, segmented myotomal muscles are the primary power source, driving undulations of the body axis that transfer momentum to the water. Multiple fins and the associated fin muscles also contribute to thrust production, and stabilization and control of the swimming trajectory. We have used blood flow tracers in swimming rainbow trout (Oncorhynchus mykiss) to estimate the regional distribution of energy use across the myotomal and fin muscle groups to reveal the functional distribution of metabolic energy use within a swimming animal for the first time. Energy use by the myotomal muscle increased with speed to meet thrust requirements, particularly in posterior myotomes where muscle power outputs are greatest. At low speeds, there was high fin muscle energy use, consistent with active stability control. As speed increased, and fins were adducted, overall fin muscle energy use declined, except in the caudal fin muscles where active fin stiffening is required to maintain power transfer to the wake. The present data were obtained under steady-state conditions which rarely apply in natural, physical environments. This approach also has potential to reveal the mechanical factors that underlie changes in locomotor cost associated with movement through unsteady flow regimes.     

An EMG-driven model applied for predicting metabolic energy consumption during movement

The relationship between mechanical work and metabolic energy cost during movement is not yet clear. Many studies demonstrated the utility of forward-dynamic musculoskeletal models combined with experimental data to address such question. The aim of this study was to evaluate the applicability of a muscle energy expenditure model at whole body level, using an EMG-driven approach.Four participants performed a 5-min squat exercise on unilateral leg press at two different frequencies and two load levels. Data collected were kinematics, EMG, forces and moments under the foot and gas-exchange data. This same task was simulated using a musculoskeletal model, which took EMG and kinematics as inputs and gave muscle forces and muscle energetics as outputs. Model parameters were taken from literature, but maximal isometric muscle force was optimized in order to match predicted joint moments with measured ones. Energy rates predicted by the model were compared with energy consumption measured by the gas-exchange data.Model results on metabolic energy consumption were close to the values obtained through indirect calorimetry. At the higher frequency level, the model underestimated measured energy consumption. This underestimation can be explained with an increase in energy consumption of the non-muscular mass with movement velocity.In conclusion, results obtained in comparing model predictions with experimental data were promising. More research is needed to evaluate this way of computing mechanical and metabolic work.     

New parameters reducing the interindividual variability of metabolic changes during muscle contraction in humans. A (31)P MRS study with physiological and clinical implications

Interindividual variations in skeletal muscle metabolism make comparative analyses difficult. In this study, we have addressed the issue of capturing the variability of metabolic performance observed during muscle exercise in humans by using an original method of normalization.Metabolic changes induced by various kinds of exercise were investigated using 31P magnetic resonance spectroscopy (MRS) at 4.7 T in 65 normal subjects (23 women and 42 men) and 12 patients with biopsy-proven muscular disorders.Large variations in the extent of PCr breakdown and intracellular acidosis were recorded among subjects and exercise protocols. For all the data pooled, the amplitude of mechanical performance accounts for 50% of these variations. When scaled to the work output, variations of PCr consumption account for 65% of pH changes through a linear relationship. This linear relationship was substantially improved (90%) when both variables were scaled to the square of work output performed (P1 and P2). By capturing most of the initial interindividual variability (90%), P1 vs. P2 relationship represents an ideal standardization procedure, independent of any anthropometric measurements. This relationship also discloses a significant link between the extent of PCr breakdown and intracellular acidosis regardless of exercise protocol. Moreover, changes in the slope of the P1 vs. P2 regression curve, as measured in old subjects and in selected patients, directly reflect alterations of energy production in muscle.     

Muscle pump function during locomotion: mechanical coupling of stride frequency and muscle blood flow

We imposed opposing oscillations in treadmill speed and grade on nine rats to test for direct mechanical coupling between stride frequency and hindlimb blood flow. Resting hindlimb blood flow was 15.5 +/- 1.7 ml/min. For 90 s at 7.5 m/min, rats alternated walking at -10 degrees for 10 s and +10 degrees for 10 s. This elicited oscillations in hindlimb blood flow having an amplitude of 4.1 +/- 0.5 ml/min (18% of mean flow) with a delay presumably due to metabolic vasodilation. Similar oscillations in speed (5.5-9.5 m/min) elicited oscillations in hindlimb blood flow (amplitude 3.4 +/- 0.5 ml/min, 15% of mean flow) with less of a delay, possibly due to changes in vasodilation and muscle pump function. We then simultaneously imposed these speed and grade oscillations out of phase (slow uphill, fast downhill). The rationale was that the oscillations in vasodilation evoked by the opposing oscillations in speed and grade would cancel each other, thereby testing the degree to which stride frequency affects hindlimb blood flow directly (i.e., muscle pumping). Opposing oscillations in speed and grade evoked oscillations in hindlimb blood flow having an amplitude of 3.3 +/- 0.6 ml/min (16% of mean flow) with no delay and directly in phase with the changes in speed and stride frequency. The finding that hindlimb blood flow changes directly with speed (when vasodilation caused by changes in speed and grade oppose each other) indicates that there is a direct coupling of stride frequency and hindlimb blood flow (i.e., muscle pumping).     

Passive leg movement enhances interstitial VEGF protein, endothelial cell proliferation, and eNOS mRNA content in human skeletal muscle

The present study used passive limb movement as an experimental model to study the effect of increased blood flow and passive stretch, without enhanced metabolic demand, in young healthy male subjects. The model used was 90 min of passive movement of the leg leading to a 2.8-fold increase (P < 0.05) in blood flow without a significant enhancement in oxygen uptake. Muscle interstitial fluid was sampled with microdialysis technique and analyzed for vascular endothelial growth factor (VEGF) protein and for the effect on endothelial cell proliferation. Biopsies obtained from the musculus vastus lateralis were analyzed for mRNA content of VEGF, endothelial nitric oxide synthase (eNOS), and matrix metalloproteinase-2 (MMP-2). The passive leg movement caused an increase (P < 0.05) in interstitial VEGF protein concentration above rest (73 +/- 21 vs. 344 +/- 83 pg/ml). Addition of muscle dialysate to cultured endothelial cells revealed that dialysate obtained during leg movement induced a 3.2-fold higher proliferation rate (P < 0.05) than dialysate obtained at rest. Passive movement also enhanced (P < 0.05) the eNOS mRNA level fourfold above resting levels. VEGF mRNA and MMP-2 mRNA levels were unaffected. The results show that a session of passive leg movement, elevating blood flow and causing passive stretch, augments the interstitial concentrations of VEGF, the proliferative effect of interstitial fluid, and eNOS mRNA content in muscle tissue. We propose that enhanced blood flow and passive stretch are positive physiological stimulators of factors associated with capillary growth in human muscle.     

Role of NADH/NAD+ transport activity and glycogen store on skeletal muscle energy metabolism during exercise: in silico studies

Skeletal muscle can maintain ATP concentration constant during the transition from rest to exercise, whereas metabolic reaction rates may increase substantially. Among the key regulatory factors of skeletal muscle energy metabolism during exercise, the dynamics of cytosolic and mitochondrial NADH and NAD+ have not been characterized. To quantify these regulatory factors, we have developed a physiologically based computational model of skeletal muscle energy metabolism. This model integrates transport and reaction fluxes in distinct capillary, cytosolic, and mitochondrial domains and investigates the roles of mitochondrial NADH/NAD+ transport (shuttling) activity and muscle glycogen concentration (stores) during moderate intensity exercise (60% maximal O2 consumption). The underlying hypothesis is that the cytosolic redox state (NADH/NAD+) is much more sensitive to a metabolic disturbance in contracting skeletal muscle than the mitochondrial redox state. This hypothesis was tested by simulating the dynamic metabolic responses of skeletal muscle to exercise while altering the transport rate of reducing equivalents (NADH and NAD+) between cytosol and mitochondria and muscle glycogen stores. Simulations with optimal parameter estimates showed good agreement with the available experimental data from muscle biopsies in human subjects. Compared with these simulations, a 20% increase (or approximately 20% decrease) in mitochondrial NADH/NAD+ shuttling activity led to an approximately 70% decrease (or approximately 3-fold increase) in cytosolic redox state and an approximately 35% decrease (or approximately 25% increase) in muscle lactate level. Doubling (or halving) muscle glycogen concentration resulted in an approximately 50% increase (or approximately 35% decrease) in cytosolic redox state and an approximately 30% increase (or approximately 25% decrease) in muscle lactate concentration. In both cases, changes in mitochondrial redox state were minimal. In conclusion, the model simulations of exercise response are consistent with the hypothesis that mitochondrial NADH/NAD+ shuttling activity and muscle glycogen stores affect primarily the cytosolic redox state. Furthermore, muscle lactate production is regulated primarily by the cytosolic redox state.     

Bond graph simulation of skeletal muscle glucose metabolism.

A mathematical model of skeletal muscle glucose metabolism is presented. This model resulted from the application of thermodynamics combined with the dynamics of an energy storage capability. The physiological system consists of the insulin modulated, carrier-mediated transport of glucose into skeletal muscle, the biochemical reactions of the Embden-Meyerhof pathway, the cyclic 3′,5′ adenosine monophosphate-dependent protein kinase controlled synthesis/degradation of glycogen stores, and the diffusion of lactate from muscle. The metabolic system is defined and synthesized by the construction of the energy flow bond graph.The bond graph model was evaluated by simulating the system response over a 2 min period to step increases in extracellular epinephrine concentration. The simulated response of the metabolites and modulated enzymes corresponds, qualitatively and quantitatively, with in vivo measurements published in the literature.     

Changes in muscle pH following hyperthermia

Considerable attention has been paid to the modification of intratumor pH in response to hyperthermia. It has been hypothesized that observed reductions in intralesional pH are involved in the ultimate response of tissue to hyperthermia treatment. Further, it has been shown that significant differences exist in hyperthermia-induced changes in blood flow between tumor and normal tissue in many systems. Changes in blood flow are hypothesized to be related to observed changes in pH. Since reduced blood flow is not observed in normal tissue under normal treatment conditions, changes in pH in normal tissue have not been considered significant in their response to hyperthermia treatment. However, this conclusion has not been verified or documented experimentally. The purpose of this study was to examine the distribution of pH in normal tissue (muscle) as a function of time following hyperthermia treatments which in the same animal system resulted in subcurative (TCD 10/30) or curative (TCD 90/30) tumor (mammary adenocarcinoma) responses. The observed distribution of pH in normal tissue was compared with that obtained in tumors under identical conditions. The results indicate that some post-treatment changes in muscle pH do occur following hyperthermia, but that these changes are small compared to those observed in tumors. More importantly, unlike the response observed in tumors, no hyperthermia dose dependency is observed in the muscle response. From these studies it can be concluded that changes in normal muscle pH are probably not associated with normal tissue response to hyperthermia.     

Human muscle length-dependent changes in blood flow

Although a multitude of factors that influence skeletal muscle blood flow have been extensively investigated, the influence of muscle length on limb blood flow has received little attention. Thus the purpose of this investigation was to determine if cyclic changes in muscle length influence resting blood flow. Nine healthy men (28 ± 4 yr of age) underwent a passive knee extension protocol during which the subjects' knee joint was passively extended and flexed through 100-180° knee joint angle at a rate of 1 cycle per 30 s. Femoral blood flow, cardiac output (CO), heart rate (HR), stroke volume (SV), and mean arterial pressure (MAP) were continuously recorded during the entire protocol. These measurements revealed that slow passive changes in knee joint angle did not have a significant influence on HR, SV, MAP, or CO; however, net femoral blood flow demonstrated a curvilinear increase with knee joint angle (r(2) = 0.98) such that blood flow increased by ～90% (125 ml/min) across the 80° range of motion. This net change in blood flow was due to a constant antegrade blood flow across knee joint angle and negative relationship between retrograde blood flow and knee joint angle (r(2) = 0.98). Thus, despite the absence of central hemodynamic changes and local metabolic factors, blood flow to the leg was altered by changes in muscle length. Therefore, when designing research protocols, researchers need to be cognizant of the fact that joint angle, and ultimately muscle length, influence limb blood flow.     

Blood flow in thigh muscle during bicycling exercise at varying work rates.

16 male subjects exercised at 25, 50, 75, 90, 100 and 120% of VO2max on a von D?beln bicycle ergometer. The muscle mass was measured in a whole body counter. Muscle blood flow (MBF) estimated from the rate of 133Xe clearance from m. rectus femoris showed a levelling-off at about 0.5 1 of blood per min and liter of muscle tissue (equal to an irrigation coefficient of 0.5 min-1) at work rates above 50 to 60% of VO2 max. This concurs with clearance data from the literature. However, when MBF is calculated from VO2, muscle mass, and reliable values for a- vo2 differences, MBF in the present subjects would: 1. Not level off before 90 to 100% VO2max, 2. reach a value of 1.0 min-1. The underestimation of MBF calculated from 133Xe clearance and the levelling-off shown by this method may be due to a systematic error inherent in the method, the 133Xe clearance being diffusion limited at high flow rates.     

The diving paradox: new insights into the role of the dive response in air-breathing vertebrates

When aquatic reptiles, birds and mammals submerge, they typically exhibit a dive response in which breathing ceases, heart rate slows, and blood flow to peripheral tissues is reduced. The profound dive response that occurs during forced submergence sequesters blood oxygen for the brain and heart while allowing peripheral tissues to become anaerobic, thus protecting the animal from immediate asphyxiation. However, the decrease in peripheral blood flow is in direct conflict with the exercise response necessary for supporting muscle metabolism during submerged swimming. In free diving animals, a dive response still occurs, but it is less intense than during forced submergence, and whole-body metabolism remains aerobic. If blood oxygen is not sequestered for brain and heart metabolism during normal diving, then what is the purpose of the dive response? Here, we show that its primary role may be to regulate the degree of hypoxia in skeletal muscle so that blood and muscle oxygen stores can be efficiently used. Paradoxically, the muscles of diving vertebrates must become hypoxic to maximize aerobic dive duration. At the same time, morphological and enzymatic adaptations enhance intracellular oxygen diffusion at low partial pressures of oxygen. Optimizing the use of blood and muscle oxygen stores allows aquatic, air-breathing vertebrates to exercise for prolonged periods while holding their breath.     

A theory of blood flow in skeletal muscle

A theoretical analysis of blood flow in the microcirculation of skeletal muscle is provided. The flow in the microvessels of this organ is quasi steady and has a very low Reynolds number. The blood is non-Newtonian and the blood vessels are distensible with viscoelastic properties. A formulation of the problem is provided using a viscoelastic model for the vessel wall which was recently derived from measurements in the rat spinotrapezius muscle (Skalak and Schmid-Sch?nbein, 1986b). Closed form solutions are derived for several physiologically important cases, such as perfusion at steady state, transient and oscillatory flows. The results show that resting skeletal muscle has, over a wide range of perfusion pressures an almost linear pressure-flow curve. At low flow it exhibits nonlinearities. Vessel distensibility and the non-Newtonian properties of blood both have a strong influence on the shape of the pressure-flow curve. During oscillatory flow the muscle exhibits hysteresis. The theoretical results are in qualitative agreement with experimental observations.     

A model of brain circulation and metabolism: NIRS signal changes during physiological challenges

We construct a model of brain circulation and energy metabolism. The model is designed to explain experimental data and predict the response of the circulation and metabolism to a variety of stimuli, in particular, changes in arterial blood pressure, CO(2) levels, O(2) levels, and functional activation. Significant model outputs are predictions about blood flow, metabolic rate, and quantities measurable noninvasively using near-infrared spectroscopy (NIRS), including cerebral blood volume and oxygenation and the redox state of the Cu(A) centre in cytochrome c oxidase. These quantities are now frequently measured in clinical settings; however the relationship between the measurements and the underlying physiological events is in general complex. We anticipate that the model will play an important role in helping to understand the NIRS signals, in particular, the cytochrome signal, which has been hard to interpret. A range of model simulations are presented, and model outputs are compared to published data obtained from both in vivo and in vitro settings. The comparisons are encouraging, showing that the model is able to reproduce observed behaviour in response to various stimuli.     

The regulation of endogeneous energy stores during starvation and refeeding in the somatic tissues of the golden perch

Adult golden perch Macquaria ambigua were fed to satiety, starved for up to 210 days, or starved for 150 days then fed to satiety for 60 days to investigate the utilization of energy stores in response to food deprivation and re-feeding. Golden perch sequentially mobilize energy from hepatic tissue, extra-hepatic lipid, and finally muscle components in response to food deprivation. The relative size of the liver was significantly reduced by 30 days after the onset of food deprivation due to the simultaneous mobilization of lipid, protein and glycogen reserves. These stores were renewed rapidly within 30 days by satiety feeding. Mobilization of lipid stores in perivisceral fat bodies occurred between 30 and 60 days of food deprivation. These deposits were also renewed upon re-feeding, although not as rapidly as liver reserves. The glycogen content of the epaxial muscle was reduced by the 60th day of food deprivation but subsequently increased indicating the mobilization of other energy reserves. The concentration of muscle lipid decreased after 90 days of food deprivation. The only significant response in body composition observed in the fish fed to satiety throughout the study was an increase in the relative size of the perivisceral fat bodies. The results of this study suggest that golden perch are well adapted to cope with extended periods of food deprivation, storing energy as perivisceral fat when food is readily available and having a clearly sequential process for mobilizing energy when food is scarce which largely protects the integrity of the musculature.     

Differential response of rat skeletal muscle glycogen metabolism to testosterone and estradiol.

Although reports on sex steroids have implicated them as promoting protein synthesis and also providing extra strength to the skeletal muscle, it remains unclear whether sex steroids affect glycogen metabolism to provide energy for skeletal muscle functions, since glycogen metabolism is one of the pathways that provides energy for the skeletal muscle contraction and relaxation cycle. The purpose of the current study was to show that testosterone and estradiol act differentially on skeletal muscles from different regions, differentially with reference to glycogen metabolism. To study this hypothesis, healthy mature male Wistar rats (90-120 days of age, weighing about 180-200 g) were castrated (a bilateral orchidectomy was performed to test the significance of skeletal muscle glycogen metabolism in the absence of testosterone). One group of castrated rats was supplemented with testosterone (100 microg/100 g body weight, i.m., for 30 days from day 31 postcastration onwards). To test whether estradiol has any effect on male skeletal muscle glycogen metabolism 17beta-estradiol (5 microg/100 g body weight, i.m., for 30 days from day 31 postcastration onwards) was administered to orchidectomized rats. To test whether these sex steroids have any differential effect on skeletal muscles from different regions, skeletal muscles from the temporal region (temporalis), muscle of mastication (masseter), forearm muscle (triceps and biceps), thigh muscle (vastus lateralis and gracilis), and calf muscle (gastrocnemius and soleus) were considered. Castration enhanced blood glucose levels and decreased glycogen stores in skeletal muscle from head, jaw, forearm, thigh, and leg regions. This was accompanied by diminished activity of glycogen synthetase and enhanced activity of muscle phosphorylase. Following testosterone supplementation to castrated rats, a normal pattern of all these parameters was maintained. Estradiol administration to castrated rats did not bring about any significant alteration in any of the parameters. The data obtained suggest a stimulatory effect of testosterone on skeletal muscle glycogenesis and an inhibitory effect on glycogenolysis. Estradiol did not play any significant role in the skeletal muscle glycogen metabolism of male rats.