Estudos Myostatina

The myostatin gene: physiology and pharmacological relevance. - Joulia-Ekaza D - Curr Opin Pharmacol - 01-JUN-2007; 7(3): 310-5 (From NIH/NLM MEDLINE) Abstract: Myostatin, which was cloned in 1997, is a potent inhibitor of skeletal muscle growth and member of the tumour growth factor-beta family. Disruption of the myostatin gene in mice induces a dramatic increase in muscle mass, caused by a combination of hypertrophy and hyperplasia. Natural mutations occurring in cattle were also associated with a significant increase in muscle mass and, recently, an inactivating myostatin mutation associated with the same phenotype was identified in humans. Studies into the molecular basis of this antimyogenic influence led to the conclusion that myostatin inhibits myoblast proliferation and differentiation through a classical tumour growth factor-beta pathway involving the activin receptor ActRIIB and Smads 2 and 3. Approaches that induce myostatin depletion or inactivation have led to a significant improvement in muscle regeneration processes, especially in degenerative diseases, through stimulation of satellite cell proliferation and differentiation. These promising data open the way to new therapeutic approaches in muscle diseases through targeting of the myostatin pathway.

Repeated resistance exercise training induces different changes in mRNA expression of MAFbx and MuRF-1 in human skeletal muscle. Mascher H, Tannerstedt J, Brink-Elfegoun T, Ekblom B, Gustafsson T, Blomstrand E. Astrand Laboratory, Swedish School of Sport and Health Sciences, Karolinska University Hospital, Karolinska Institutet, Box 5626, Stockholm, S-114 86, Sweden. The gain in muscle mass as a result of resistance training is dependent on changes in both anabolic and catabolic reactions. A frequency of two to three exercise sessions per week is considered optimal for muscle gain in untrained individuals. Our hypothesis was that a second exercise session would enlarge the anabolic response and/or decrease the catabolic response. Eight male subjects performed resistance exercise on two occasions separated by 2 days. Muscle biopsies were taken from the vastus lateralis before and 15 min, 1 h, and 2 h after exercise. Exercise led to severalfold increases in phosphorylation of mTOR at Ser2448, p70 S6 kinase (p70S6k) at Ser424/Thr421 and Thr389, and ribosomal protein S6, which persisted for up to 2 h of recovery on both occasions. There was a tendency toward a larger effect of the second exercise on p70S6k and S6, but the difference did not reach statistical significance. The mRNA expression of MuRF-1, which increased after exercise, was 30% lower after the second exercise session than after the first one. MAFbx expression was not altered after exercise but downregulated 30% 48 h later, whereas myostatin expression was reduced by 45% after the first exercise and remained low until after the second exercise session. The results indicate that 1) changes in expression of genes involved in protein degradation are attenuated as a response to repetitive resistance training with minor additional increases in enzymes regulating protein synthesis and 2) the two ubiquitin ligases, MuRF-1 and MAFbx, are differently affected by the exercise as well as by repeated exercise.

Postexercise myostatin and activin IIb mRNA levels: effects of strength training. Hulmi JJ, Ahtiainen JP, Kaasalainen T, P�ll�nen E, H�kkinen K, Alen M, Sel�nne H, Kovanen V, Mero AA.

Department of Biology of Physical Activity and Neuromuscular Research Center, University of Jyv�skyl�, Jyv�skyl�, Finland. [email protected] PURPOSE: Muscle hypertrophy is likely to result from the cumulative effects of repeated bouts of resistance exercise (RE) on postexercise molecular responses. Therefore, we determined muscle growth- and regeneration-related mRNA expression in response to a single RE bout both before and after a strength-training (ST) period. By means of this novel longitudinal setting, we examined whether postexercise gene expression at the transcriptional level is different in the trained and untrained state. METHODS: Eleven untrained healthy older men and 11 controls (age 62.3 +/- 6.3 yr) volunteered as subjects. Muscle biopsies from the vastus lateralis muscle were taken at rest and 1 and 48 h after five sets of 10repetition leg press RE both before and after 21 wk of supervised ST. RESULTS: Myostatin and myogenin mRNA expression, determined by real-time RT-PCR, increased (P < 0.05) after ST. Conversely, the single RE bout decreased myostatin mRNA after ST, with the decrease showing a negative correlation (r = -0.65, P < 0.05) with the long-term increase in myostatin during ST. Furthermore, RE before ST increased myogenin mRNA (P < 0.05) and tended to increase after ST (P = 0.08). Myostatin receptor activin IIb mRNA levels were decreased at 1 h after RE in the pre-ST condition (P = 0.05) and also tended to decrease in the post-ST condition (P = 0.07). RE-induced downregulation in myostatin mRNA correlated with the ST-induced increase in total body muscle mass (r = -0.82, P = 0.002). CONCLUSIONS: A single bout of RE in older men can downregulate the expression of myostatin receptor activin IIb mRNA. ST influences the response of myostatin to RE, as short-term REinduced downregulation of myostatin was observed only after ST. The results also indicate that RE-induced alterations in myostatin mRNA expression may have a role in ST-induced muscle hypertrophy. Effect of swimming on myostatin expression in white and red gastrocnemius muscle and in cardiac muscle of rats. - Matsakas A - Exp Physiol - 01-NOV-2006; 91(6): 983-94 (From NIH/NLM MEDLINE) Abstract: The aim of this study was to test the hypothesis that swimming training might impact differentially myostatin expression in skeletal muscles, depending on fibre type composition, and in cardiac muscle of rats. Myostatin expression was analysed by real time reverse transcriptase-polymerase chain reaction, Western blot and immunohistochemistry of the red deep portion (mainly composed of slow and type II A fibres) and in the superficial, white portion (composed of fast type II X and II B fibres) of the gastrocnemius muscle in adult male Wistar rats: (i) subjected to two consecutive swimming bouts for 3 h; (ii) subjected to intensive swimming training for 4 weeks; and (iii) sedentary control rats. Myostatin mRNA content was in all cases higher in white than in red muscles. Two bouts of swimming did not alter myostatin expression, whereas swimming training for 4 weeks resulted in a significant reduction of myostatin mRNA contents, significant both in white and red muscles but more pronounced in white muscles. Western blot did not detect any change in the amount of myostatin protein. Immunohistochemistry showed that, in control rats, myostatin was localized in presumptive satellite cells of a few muscle fibres. After training, the number of myostatin-positive spots decreased significantly. Myostatin mRNA content in cardiac muscle was lower than in skeletal muscle and was significantly increased by swimming training. In conclusion, the results obtained showed that intense training caused a decreased expression of myostatin mRNA in white and red skeletal muscles but an increase in cardiac muscle.

Short-term endurance training results in a muscle-specific decrease of myostatin mRNA content in the rat. Matsakas A, Friedel A, Hertrampf T, Diel P. Department of Molecular and Cellular Sports Medicine, German Sport University Cologne, Carl-Diem-Weg 6, 50933 Cologne, Germany. AIM: Myostatin has been characterized as a negative regulator of skeletal muscle growth. To examine a probable function of myostatin during the adaptation of skeletal muscle in response to training, we analysed the effect of short-term endurance training on myostatin and insulin-like growth factor-I (IGF-I) mRNA contents in rat skeletal muscles. To assess the impact of the training stimulus, mRNA levels of metabolic genes were analysed simultaneously. METHODS: Male Wistar rats were trained for 5 days by swimming, while another group remained untrained. Myostatin, IGF-I, glucose transporter 4 (GLUT4), hexokinase II (HK II) and hydroxyacyl-CoA dehydrogenase (HAD) mRNA levels were determined by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in gastrocnemius, vastus lateralis and soleus muscles. A time course experiment was conducted, in order to examine transient changes of myostatin mRNA contents in gastrocnemius 7 and 24 h after one-swimming session as well as 24 h after a 3-day swimming training. RESULTS: No significant changes in IGF-I and GLUT4 mRNA levels were found in any of the muscles analysed. mRNA contents of myostatin were significantly reduced in gastrocnemius and vastus lateralis but not in soleus. In agreement to this pattern, we found significantly higher mRNA levels of HK II and HAD in the trained group. The time course experiment revealed significantly reduced myostatin mRNA contents in gastrocnemius 7 but not 24 h post-exercise. The 3-day swimming training resulted also in significantly lower myostatin mRNA levels in the trained group. CONCLUSION: This study demonstrated that short-term endurance training may modulate myostatin mRNA levels, implying a probable role of myostatin in remodelling of skeletal muscle in response to training. Myostatin gene expression is reduced in humans with heavy-resistance strength training: a brief communication. Roth SM, Martel GF, Ferrell RE, Metter EJ, Hurley BF, Rogers MA. Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA. sroth [email protected] This study examined changes in myostatin gene expression in response to strength training (ST). Fifteen young and older men (n = 7) and women (n = 8) completed a 9-week heavy-resistance unilateral knee extension ST program. Muscle biopsies were obtained from the dominant vastus lateralis before and after ST. In addition to myostatin mRNA levels, muscle volume and strength were measured. Total RNA was reverse transcribed into cDNA, and myostatin mRNA was quantified using quantitative PCR by standard fluorescent chemistries and was normalized to 18S rRNA levels. A 37% decrease in myostatin expression was observed in response to ST in all subjects combined (2.70 +/- 0.36 vs 1.69 +/- 0.18 U, arbitrary units; P < 0.05). Though the decline in myostatin expression was similar regardless of age or gender, the small number of subjects in these subgroups suggests that this observation needs to be confirmed. No significant correlations were observed between myostatin expression and any muscle strength or volume measure. Although further work is necessary to clarify the findings, these data demonstrate that myostatin mRNA levels are reduced in response to heavy-resistance ST in humans. Human muscle gene expression following resistance exercise and blood flow

restriction. Drummond MJ, Fujita S, Abe T, Dreyer HC, Volpi E, Rasmussen BB. Department of Physical Therapy, University of Texas Medical Branch, Galveston, TX, USA. INTRODUCTION: Blood flow restriction in combination with low-intensity resistance exercise (REFR) increases skeletal muscle size to a similar extent as compared with traditional high-intensity resistance exercise training. However, there are limited data describing the molecular adaptations that occur after REFR. PURPOSE: To determine whether hypoxia inducible factor-1 alpha (HIF-1alpha) and REDD1 mRNA are expressed differently in REFR compared with low-intensity resistance exercise with no blood flow restriction (CONTROL). Secondly, to determine whether lowintensity resistance exercise is able to induce changes in mRNA expression of several anabolic and catabolic genes as typically seen with high-intensity resistance exercise. METHODS: Six subjects were studied at baseline and 3 h after a bout of leg resistance exercise (20% 1RM) in REFR and CONTROL subjects. Each subject participated in both groups, with 3 wk separating each visit. Muscle biopsy samples were analyzed for mRNA expression, using qRT-PCR. RESULT: Our primary finding was that there were no differences between CONTROL and REFR for any of the selected genes at 3 h after exercise (P > 0.05). However, low-intensity resistance exercise increased HIF-1alpha, p21, MyoD, and muscle RING finger 1 (MuRF1) mRNA expression and decreased REDD1 and myostatin mRNA expression in both groups (P < 0.05). CONCLUSION: Low-intensity resistance exercise can alter skeletal muscle mRNA expression of several genes associated with muscle growth and remodeling, such as REDD1, HIF-1alpha, MyoD, MuRF1, and myostatin. Further, the results from REFR and CONTROL were similar, indicating that the changes in early postexercise gene expression were attributable to the low-intensity resistance exercise bout, and not blood flow restriction. Effects of resistance exercise with and without creatine supplementation on gene expression and cell signaling in human skeletal muscle. Deldicque L, Atherton P, Patel R, Theisen D, Nielens H, Rennie MJ, Francaux M. Place Pierre de Coubertin 1, B-1348 Louvain-la-Neuve, Belgium. To test the hypothesis that creatine supplementation would enhance the anabolic responses of muscle cell signaling and gene expression to exercise, we studied nine subjects who received either creatine or a placebo (maltodextrin) for 5 days in a double-blind fashion before undergoing muscle biopsies: at rest, immediately after exercise (10 x 10 repetitions of one-leg extension at 80% 1 repetition maximum), and 24 and 72 h later (all in the morning after fasting overnight). Creatine supplementation decreased the phosphorylation state of protein kinase B (PKB) on Thr308 at rest by 60% (P < 0.05) and that of eukaryotic initiation factor 4E-binding protein on Thr37/46 (4E-BP1) by 30% 24 h postexercise (P < 0.05). Creatine increased mRNA for collagen 1 (alpha(1)), glucose transporter-4 (GLUT-4), and myosin heavy chain I at rest by 250%, 45%, and 80%, respectively, and myosin heavy chain IIA (MHCIIA) mRNA immediately after exercise by 70% (all P < 0.05). Immediately after exercise, and independent of creatine, mRNA for muscle atrophy F-box (MAFbx), MHCIIA, peroxisome proliferator-activated receptor gamma coactivator-1alpha, and interleukin-6 were upregulated (60-350%; P < 0.05); the phosphorylation state of p38 both in the sarcoplasm and nucleus were increased (12- and 25-fold, respectively; both P < 0.05). Concurrently, the phosphorylation states of PKB (Thr308) and 4E-BP1 (Thr37/46) were decreased by 50% and 75%, respectively (P < 0.05). Twenty-four hours postexercise, MAFbx, myostatin, and GLUT-4 mRNA expression decreased below preexercise values (-35 to -50%; P < 0.05); calpain 1 mRNA increased 70% 72 h postexercise (P < 0.05) and at no other time. In

conclusion, 5 days of creatine supplementation do not enhance anabolic signaling but increase the expression of certain targeted genes.

The effects of whey protein on myostatin and cell cycle-related gene expression responses to a single heavy resistance exercise bout in trained older men. Hulmi JJ, Kovanen V, Lisko I, Sel�nne H, Mero AA. Department of Biology of Physical Activity, University of Jyv�skyl�, P.O. Box 35, 40014, Jyv�skyl�, Finland, [email protected]. Myostatin decreases muscle mass and this is accomplished, in part, by inhibiting muscle satellite cell proliferation and differentiation by regulating the expression of cell cycle-related proteins (e.g. p21 and cdk2) and myogenic regulatory factors (e.g. myogenin and MyoD). The purpose of this investigation was to determine whether protein ingestion before and after a resistance exercise (RE) bout affects myostatin and cell cycle-related gene expression. Strength-trained middle-aged to older men were divided into a protein group (61.4 +/- 4.3 years, n = 9) or a placebo group (62.1 +/- 4.2 years, n = 9). Muscle biopsies from the vastus lateralis muscle were taken at rest and 1 and 48 h after a 5 x 10 repetition leg press RE bout. Protein (15 g whey) or non-caloric placebo was taken immediately before and after the RE bout. mRNA expression levels of myostatin and related genes (AcvrIIb, FLRG, p21, p27, cdk2, myogenin and MyoD) were determined by Taqman probe-based real-time RT-PCR and normalized to GAPDH mRNA. Myostatin mRNA decreased after a RE bout, but only in the placebo group (P
Impact of repeated bouts of eccentric exercise on myogenic gene expression. Costa A, Dalloul H, Hegyesi H, Apor P, Csende Z, Racz L, Vaczi M, Tihanyi J. Department of Biomechanics, Faculty of Physical Education and Sport Sciences, Semmelweis University, Budapest, Hungary. Evidence indicates that repeated-bouts of eccentric exercise (EE) do not exacerbate the extent of muscle damage indices, as compared to a single-bout. We hypothesized that molecular adaptations, under repeated-bouts of EE, would include suppression of muscle repair inhibitory factors such as myostatin and upregulation of muscle repair positive regulatory factors such as myogenic regulatory factors (MRFs). Fifteen males were recruited for this study. The exercise group (n=9) successfully completed six sets of 15 reps of maximum voluntary eccentric contractions, for six consecutive days, using a dynamometer (Multicont-II). Blood and muscle biopsy samples were obtained from each subject 1 week prior to exercise, 2 days post the first training session, and 24 h after the last training session. Gene expression levels were determined using real-time RTPCR. Blood samples were analyzed for creatine kinase (CK) and lactatedehydrogenase (LDH) activity. Repeated-bouts of EE induced a large down-regulation of myostatin mRNA (-73%) which persisted throughout the study. The responses of MRFs were mild. At day 3 only myogenin increased significantly (1.9 fold) while

MyoD decreased by 45%. Surprisingly, at day 7, despite the presence of muscle damage indices, all MRFs returned to the pre-exercise levels. The results of the present study showed that repeated-bouts of EE, for six consecutive days, dramatically decreased Myostatin mRNA expression but impaired the expression patterns of MRFs such that, with the exception of myogenin that showed a moderate non-sustained increase, MyoD and MYf5 response was minimal. Short-term strength training and the expression of myostatin and IGF-I isoforms in rat muscle and tendon: differential effects of specific contraction types. Heinemeier KM, Olesen JL, Schjerling P, Haddad F, Langberg H, Baldwin KM, Kjaer M. Institute of Sports Medicine, Bispebjerg Hospital-Bldg. 8, 1st Floor, 23 Bispebjerg Bakke, DK-2400 Copenhagen NV, Denmark. [email protected] In skeletal muscle, an increased pression of insulin like growth factor-I isoforms IGF-IEa and mechano-growth factor (MGF) combined with downregulation of myostatin is thought to be essential for training-induced hypertrophy. However, the specific effects of different contraction types on regulation of these factors in muscle are still unclear, and in tendon the functions of myostatin, IGF-IEa, and MGF in relation to training are unknown. Female Sprague-Dawley rats were subjected to 4 days of concentric, eccentric, or isometric training (n = 7-9 per group) of the medial gastrocnemius, by stimulation of the sciatic nerve during general anesthesia. mRNA levels for myostatin, IGF-IEa, and MGF in muscle and Achilles' tendon were measured by real-time RT-PCR. Muscle myostatin mRNA decreased in response to all types of training (2- to 8-fold) (P < 0.05), but the effect of eccentric training was greater than concentric and isometric training (P < 0.05). In tendon, myostatin mRNA was detected, but no changes were seen after exercise. IGF-IEa and MGF increased in muscle (up to 15-fold) and tendon (up to 4-fold) in response to training (P < 0.01). In tendon no difference was seen between training types, but in muscle the effect of eccentric training was greater than concentric training for both IGF-IEa and MGF (P < 0.05), and for IGF-IEa isometric training had greater effect than concentric (P < 0.05). The results indicate a possible role for IGF-IEa and MGF in adaptation of tendon to training, and the combined changes in myostatin and IGF-IEa/MGF expression could explain the important effect of eccentric actions for muscle hypertrophy. Click here to read Links Similar acute molecular responses to equivalent volumes of isometric, lengthening, or shortening mode resistance exercise. Garma T, Kobayashi C, Haddad F, Adams GR, Bodell PW, Baldwin KM. Department of Physiology and Biophysics, University of California, Irvine, California 92697, USA. The present study was undertaken to test the hypothesis that the contraction mode of action [static-isometric (Iso), shortening-concentric (Con), or lengthening-eccentric (Ecc)] used to stress the muscle provides a differential mechanical stimulus eliciting greater or lesser degrees of anabolic response at the initiation of a resistance training program. We performed an acute resistance training study in which different groups of rodents completed four training sessions in either the Iso, Con, or Ecc mode of contraction under conditions of activation and movement specifically designed to elicit equivalent volumes of force accumulation. The results of this experiment indicate that the three modes of contraction produced nearly identical cell signaling, indicative of an anabolic response involving factors such as increased levels of mRNA for IGF-I, procollagen III alpha1, decreased myostatin mRNA, and increased total RNA concentration. The

resulting profiles collectively provide evidence that pure mode of muscle action, in and of itself, does not appear to be a primary variable in determining the efficacy of increased loading paradigms with regard to the initiation of selected muscle anabolic responses.

Impact of resistance loading on myostatin expression and cell cycle regulation in young and older men and women. Kim JS, Cross JM, Bamman MM. UAB Dept. of Physiology and Biophysics, Muscle Research Laboratory, GRECC/11G, Veterans Affairs Medical Center, 1530 3rd Ave. South, Birmingham, AL 35294-0001, USA. Myostatin inhibits myoblast proliferation and differentiation in developing muscle. Mounting evidence suggests that myostatin also plays a limiting role in growth/repair/regeneration of differentiated adult muscle by inhibiting satellite cell activation. We tested the hypothesis that myostatin mRNA expression would decrease after resistance loading (RL) with a blunted response in older (O) females (F) who have shown minimal hypertrophy [vs. males (M)] after long-term RL. As myostatin is thought to modulate cell cycle activity, we also studied the response of gene transcripts key to stimulation (cyclin B1 and D1) and inhibition (p21cip and p27kip) of the cell cycle, along with the muscle-specific loadsensitive mitogen mechano-growth factor (MGF). Twenty young (Y; 20-35 yr, 10 YF, 10 YM) and 18 O (60-75 yr, 9 OF, 9 OM) consented to vastus lateralis biopsy before and 24 h after a bout of RL (3 sets x 8-12 repetitions to volitional fatigue of squat, leg press, knee extension). Gene expression levels were determined by relative RT-PCR with 18S as an internal standard and analyzed by age x gender x load repeated-measures ANOVA. A load effect was found for four transcripts (P < 0.005) including myostatin, cyclin D1, p27kip, and MGF as mRNA levels decreased for myostatin (-44%) and p27kip (-16%) and increased for cyclin D1 (34%) and MGF (49%). For myostatin, age x load and gender x load interactions (P < 0.05) were driven by a lack of change in OF, while marked declines were noted in YM (-56%), YF (-48%), and OM (-40%). Higher cyclin D1 levels in OF led to a main age effect (36%, O > Y) and an age x gender interaction (66%, OF > YF vs. 10%, OM > YM; P < 0.05). An age x gender x load interaction (P < 0.05) for cyclin D1 resulted from a 48% increase in OF. Post hoc testing within groups revealed a significant increase in MGF after RL in YM only (91%, P < 0.05). Higher levels of cyclin B1 in O (27%, O > Y) led to a main age effect (P < 0.05). An age x load interaction for cyclin B1 (P < 0.05) was driven by a 26% increase in Y with no change in O after RL. No age or gender differences, or load-mediated changes, were detected in levels of p21cip mRNA expression. These data clearly demonstrate that RL downregulates myostatin expression and alters genes key to cell cycle progression. However, failure to reduce myostatin expression may play a role in limiting RL-induced hypertrophy in OF.

Effects of testosterone on body composition of the aging male. Mudali S, Dobs AS. Johns Hopkins University School of Medicine, Baltimore, MD 21208, USA. The aging process is accompanied by significant changes in body composition characterized by decreased fat free mass and increased and redistributed fat mass. Muscle loss results from the atrophy of muscle fibers and decreased synthesis of

muscle proteins. Increased number of adipocytes and fat accumulation in nonadipose tissue leads to adiposity. These changes can impose functional limitations and increase morbidity. In men, declining testosterone levels that occur with aging can be a contributing factor to these changes. Studies in hypogonadal men have shown that testosterone replacement is effective in increasing muscle mass and strength and decreasing fat mass. The molecular mechanisms of testosterone's influence on muscle and adipose are not fully elucidated. However, testosterone appears to stimulate IGF-1 expression directly and indirectly leading to increased muscle protein synthesis and growth. It may also counter the inhibitory effects of myostatin, cytokines, and glucocorticoids. The predominant effects of testosterone on fat mass are increased lipolysis and decreased adipogenesis. Current evidence suggests that testosterone replacement may be effective in reversing age-dependent body composition changes and associated morbidity. However, hypogonadism must be diagnosed carefully, and therapy should be monitored regularly in order to avoid the adverse effects associated with testosterone supplementation.

Myostatin regulation during skeletal muscle regeneration. Kirk S, Oldham J, Kambadur R, Sharma M, Dobbie P, Bass J. Functional Muscle Genomics, AgResearch, Ruakura Agricultural Research Centre, Hamilton, New Zealand. [email protected] Myostatin, a member of the TGF-beta superfamily, is a key negative regulator of skeletal muscle growth. The role of myostatin during skeletal muscle regeneration has not previously been reported. In the present studies, normal Sprague-Dawley and growth hormone (GH)-deficient (dw/dw) rats were administered the myotoxin, notexin, in the right M. biceps femoris on day 0. The dw/dw rats then received either saline or human-N-methionyl GH (200microg/100g body weight/day) during the ensuing regeneration. Normal and dw/dw M. biceps femoris were dissected on days 1, 2, 3, 5, 9 and 13, formalin-fixed, then immunostained for myostatin protein. Immunostaining for myostatin revealed high levels of protein within necrotic fibres and connective tissue of normal and dw/dw damaged muscles. Regenerating myotubes contained no myostatin at the time of fusion (peak fusion on day 5), and only low levels of myostatin were observed during subsequent myotube enlargement. Fibres which survived assault by notexin (survivor fibres) contained moderate to high myostatin immunostaining initially. The levels in both normal and dw/dw rat survivor fibres decreased on days 2-3, then increased on days 9-13. In dw/dw rats, there was no observed effect of GH administration on the levels of myostatin protein in damaged muscle. The low level of myostatin observed in regenerating myotubes in these studies suggests a negative regulatory role for myostatin in muscle regeneration. Copyright 2000 Wiley-Liss, Inc.

Myostatin negatively regulates satellite cell activation and self-renewal. McCroskery S, Thomas M, Maxwell L, Sharma M, Kambadur R. Animal Genomics, AgResearch, Hamilton 2015, New Zealand. Satellite cells are quiescent muscle stem cells that promote postnatal muscle growth and repair. Here we show that myostatin, a TGF-beta member, signals satellite cell quiescence and also negatively regulates satellite cell selfrenewal. BrdU labeling in vivo revealed that, among the Myostatin-deficient satellite cells, higher numbers of satellite cells are activated as compared with wild type. In contrast, addition of Myostatin to myofiber explant cultures

inhibits satellite cell activation. Cell cycle analysis confirms that Myostatin up-regulated p21, a Cdk inhibitor, and decreased the levels and activity of Cdk2 protein in satellite cells. Hence, Myostatin negatively regulates the G1 to S progression and thus maintains the quiescent status of satellite cells. Immunohistochemical analysis with CD34 antibodies indicates that there is an increased number of satellite cells per unit length of freshly isolated Mstn-/muscle fibers. Determination of proliferation rate suggests that this elevation in satellite cell number could be due to increased self-renewal and delayed expression of the differentiation gene (myogenin) in Mstn-/- adult myoblasts. Taken together, these results suggest that Myostatin is a potent negative regulator of satellite cell activation and thus signals the quiescence of satellite cells.

Prolonged underfeeding of sheep increases myostatin and myogenic regulatory factor Myf-5 in skeletal muscle while IGF-I and myogenin are repressed. Jeanplong F, Bass JJ, Smith HK, Kirk SP, Kambadur R, Sharma M, Oldham JM. Animal Genomics, New Zealand Pastoral Agriculture Research Institute, Ruakura Research Centre, Private Bag 3123, Hamilton 2020, New Zealand. The IGF axis is nutritionally sensitive in vivo and IGFs stimulate myoblast proliferation and differentiation in vitro, while myostatin inhibits these processes in vitro. We hypothesised that underfeeding would reversibly inhibit the myogenic activity of satellite cells in vivo together with decreased IGF-I and increased myostatin in muscle. Satellite cell activity was measured indirectly from the expression of proliferating cell nuclear antigen (PCNA) and the myogenic regulatory factors (MRFs), MyoD, Myf-5 and myogenin. Young sheep were underfed (30% of maintenance) and some killed after 1, 4, 12, 17, 21 and 22 weeks. Remaining underfed animals were then re-fed a control ration of pellets and killed after 2 days, and 1, 6 and 30 weeks. Expression of PCNA and MRFs decreased during the first week of underfeeding. This coincided with reduced IGF-I and myostatin mRNA, and processed myostatin. Subsequently, Myf-5, MyoD, myostatin mRNA and processed myostatin increased, suggesting that satellite cells may have become progressively quiescent. Long-term underfeeding caused muscle necrosis in some animals and IGF-I and MRF expression was increased in these, indicating the activation of satellite cells for muscle repair. Re-feeding initiated rapid muscle growth and increased expression of PCNA, IGF-I and the MRFs concurrently with decreased myostatin proteins. In conclusion, these data indicate that IGF-I and myostatin may work in a coordinated manner to regulate the proliferation, differentiation and quiescence of satellite cells in vivo.

================================================================================== ============================================ ================================================================================== ============================================ ================================================================================== ============================================ Effects of whole-body low-intensity resistance training with slow movement and tonic force generation on muscular size and strength in young men. Tanimoto M, Sanada K, Yamamoto K, Kawano H, Gando Y, Tabata I, Ishii N, Miyachi M.

Division of Health Promotion and Exercise, National Institute of Health and Nutrition, Tokyo, Japan. [email protected] Our previous study showed that relatively low-intensity (approximately 50% onerepetition maximum [1RM]) resistance training (knee extension) with slow movement and tonic force generation (LST) caused as significant an increase in muscular size and strength as high-intensity (approximately 80% 1RM) resistance training with normal speed (HN). However, that study examined only local effects of one type of exercise (knee extension) on knee extensor muscles. The present study was performed to examine whether a whole-body LST resistance training regimen is as effective on muscular hypertrophy and strength gain as HN resistance training. Thirty-six healthy young men without experience of regular resistance training were assigned into three groups (each n = 12) and performed whole-body resistance training regimens comprising five types of exercise (vertical squat, chest press, latissimus dorsi pull-down, abdominal bend, and back extension: three sets each) with LST (approximately 55-60% 1RM, 3 seconds for eccentric and concentric actions, and no relaxing phase); HN (approximately 80-90% 1RM, 1 second for concentric and eccentric actions, 1 second for relaxing); and a sedentary control group (CON). The mean repetition maximum was eight-repetition maximum in LST and HN. The training session was performed twice a week for 13 weeks. The LST training caused significant (p < 0.05) increases in whole-body muscle thickness (6.8 +/3.4% in a sum of six sites) and 1RM strength (33.0 +/- 8.8% in a sum of five exercises) comparable with those induced by HN training (9.1 +/- 4.2%, 41.2 +/7.6% in each measurement item). There were no such changes in the CON group. The results suggest that a whole-body LST resistance training regimen is as effective for muscular hypertrophy and strength gain as HN resistance training.

The influence of eccentric exercise on mRNA expression of skeletal muscle regulators. Jensky NE, Sims JK, Rice JC, Dreyer HC, Schroeder ET. Division of Biokinesiology and Physical Therapy, Clinical Exercise Research Center, University of Southern California, 1540 E. Alcazar St. CHP-155, Los Angeles, CA, 90033 USA. To evaluate change in myostatin, follistatin, MyoD and SGT mRNA gene expression using eccentric exercise to study mechanisms of skeletal muscle hypertrophy. Young (28+/-5 years) and older (68+/-6 years) men participated in a bout of maximal single-leg eccentric knee extension on an isokinetic dynamometer at 60 degrees /s: six sets, 12-16 maximal eccentric repetitions. Muscle biopsies of the vastus lateralis were obtained from the dominant leg before exercise and 24 h after exercise. Paired t tests were used to compare change (pre versus post-exercise) for normalized gene expression in all variables. Independent t tests were performed to test group differences (young vs. older). A probability level of P0.23 for all variables. Our data suggests that a single bout of maximal eccentric exercise does not alter myostatin, follistatin, MyoD or SGT mRNA gene expression in young or older subjects.

Muscular performance after concentric and eccentric exercise in trained men. Vikne H, Refsnes PE, Ekmark M, Medb� JI, Gundersen V, Gundersen K. Norwegian School of Sport Sciences, Oslo, Norway. PURPOSE: We studied previously resistance-trained men and compared the effects of concentric and eccentric training on performance and structural muscle parameters. METHODS: Seventeen trained individuals (age 26.9 +/- 3.4 yr) participated in 12 wk of either maximum concentric (N = 8) or eccentric (N = 9) resistance training of the elbow flexors. The functional performance was measured as the maximum concentric and eccentric strength and angular velocity at standard loads. Muscle cross-sectional area and cross-sectional area of single cells were used as measures of muscular hypertrophy. Fiber-type proportions were assessed by staining cells for myofibrillar ATPase. RESULTS: Both eccentric and concentric training increased concentric strength to a similar extent (14 vs 18%), whereas eccentric training led to greater increases in eccentric strength than concentric training did (26 vs 9%). The maximum angular velocity at all loads was enhanced equally in both training groups. The cross-sectional area of both the elbow flexors (+11%) and of the type I and type IIA fibers increased only after the eccentric training. In addition, the relative cross-sectional area occupied by the type II fibers increased from 64 to 73% after the eccentric training. There were only minor changes in the fiber-type proportions. CONCLUSION: The present data suggest that for resistance-trained men, increases in concentric strength and velocity performance after eccentric training are largely mediated by changes in fiber and muscle cross-sectional area. However, hypertrophy alone could not explain the increase in eccentric strength. Because the increases in strength and velocity performance after concentric training could not be ascribed to muscular adaptations alone, we suggest that they may be attributable to additional neural factors.

The effect of resistance training combined with timed ingestion of protein on muscle fiber size and muscle strength. Andersen LL, Tufekovic G, Zebis MK, Crameri RM, Verlaan G, Kjaer M, Suetta C, Magnusson P, Aagaard P. Sports Medicine Research, Unit/Team Denmark Test Center, Bispebjerg Hospital, DK2400 Copenhagen, Denmark. [email protected] Acute muscle protein metabolism is modulated not only by resistance exercise but also by amino acids. However, less is known about the long-term hypertrophic effect of protein supplementation in combination with resistance training. The present study was designed to compare the effect of 14 weeks of resistance training combined with timed ingestion of isoenergetic protein vs carbohydrate supplementation on muscle fiber hypertrophy and mechanical muscle performance. Supplementation was administered before and immediately after each training bout and, in addition, in the morning on nontraining days. Muscle biopsy specimens were obtained from the vastus lateralis muscle and analyzed for muscle fiber crosssectional area. Squat jump and countermovement jump were performed on a force platform to determine vertical jump height. Peak torque during slow (30 degrees s1) and fast (240 degrees s-1) concentric and eccentric contractions of the knee extensor muscle was measured in an isokinetic dynamometer. After 14 weeks of resistance training, the protein group showed hypertrophy of type I (18% +/- 5%; P < .01) and type II (26% +/- 5%; P < .01) muscle fibers, whereas no change above

baseline occurred in the carbohydrate group. Squat jump height increased only in the protein group, whereas countermovement jump height and peak torque during slow isokinetic muscle contraction increased similarly in both groups. In conclusion, a minor advantage of protein supplementation over carbohydrate supplementation during resistance training on mechanical muscle function was found. However, the present results may have relevance for individuals who are particularly interested in gaining muscle size. Muscle hypertrophy following 5-week resistance training using a non-gravitydependent exercise system. Tesch PA, Ekberg A, Lindquist DM, Trieschmann JT. Department of Physiology and Pharmacology, Huddinge University Hospital, Karolinska Institutet, Stockholm, Sweden. AIM: The efficacy of a mechanical, gravity-independent resistance exercise (RE) system to induce strength gains and muscle hypertrophy was validated. Designed for space crew in orbit, this technique offers resistance during coupled concentric and eccentric actions by utilizing the inertia of a rotating flywheel(s), set in motion by the trainee. METHODS: Ten middle-aged (30-53 years) men and women performed four sets of seven maximal, unilateral (left limb) knee extensions two or three times weekly for 5 weeks. Knee extensor force and electromyographic (EMG) activity of the three superficial quadriceps muscles were measured before and after this intervention. In addition, with the use of magnetic resonance imaging (MRI), volume of individual knee extensor and ankle plantar flexor muscles was assessed. RESULTS: Over the 12 training sessions, the average concentric (CON) and eccentric (ECC) force generated during exercise increased by 11% (P < 0.05). Likewise, maximal isometric strength (maximal voluntary contraction, MVC) at 90 and 120 degrees knee angle increased by (P < 0.05) 11 and 12% respectively, after training. Neither individual quadriceps muscle showed a change (P > 0.05) in maximal integrated EMG (iEMG) activity. Quadriceps muscle volume increased by 6.1% (P < 0.05). Although the magnitude of response varied, all individual quadriceps muscles showed increased (P < 0.05) volume after training. As expected, ankle plantar flexor volume of the trained limb was unchanged (P > 0.05). Likewise, MVC, CON and ECC force, iEMG and knee extensor and plantar flexor muscle volume were unaltered (P > 0.05) in the right, non-trained limb. CONCLUSION: The results of this study show that the present RE regimen produces marked muscle hypertrophy and important increases in maximal voluntary strength and appears equally effective as RE paradigms using gravity-dependent weights, in this regard.

The effects of eccentric and concentric training at different velocities on muscle hypertrophy. Farthing JP, Chilibeck PD. College of Kinesiology, University of Saskatchewan, 105 Gymnasium Place, Saskatoon, Saskatchewan, S7N 5C2, Canada. The purpose of this study was to examine the effect of isokinetic eccentric (ECC) and concentric (CON) training at two velocities [fast, 180 degrees s(-1 )(3.14 rad s(-1)) and slow,30 degrees s(-1)(0.52 rad s(-1))] on muscle hypertrophy. Twentyfour untrained volunteers (age 18-36 years) participated in fast- ( n=13) or slow( n=11) velocity training, where they trained one arm eccentrically for 8 weeks followed by CON training of the opposite arm for 8 weeks. Ten subjects served as controls (CNT). Subjects were tested before and after training for elbow flexor muscle thickness by sonography and isokinetic strength (Biodex). Overall, ECC

training resulted in greater hypertrophy than CON training (P<0.01). No significant strength or hypertrophy changes occurred in the CNT group. ECC (180 degrees s(-1)) training resulted in greater hypertrophy than CON (180 degrees s(1)) training and CON (30 degrees s(-1)) training (P<0.01). ECC (30 degrees s(-1)) training resulted in greater hypertrophy than CON (180 degrees s(-1)) training (P<0.05), but not CON (30 degrees s(-1)) training. ECC (180 degrees s(-1)) training resulted in the greatest increases in strength (P<0.01). We conclude that ECC fast training is the most effective for muscle hypertrophy and strength gain.

Selected contribution: acute cellular and molecular responses to resistance exercise. Haddad F, Adams GR. Department of Physiology and Biophysics, University of California, Irvine 92697, USA. Training protocols apply sequential bouts of resistance exercise (RE) to induce the cellular and molecular responses necessary to produce compensatory hypertrophy. This study was designed to 1) define the time course of selected cellular and molecular responses to a single bout of RE and 2) examine the effects of interbout rest intervals on the summation of these responses. Rat muscles were exposed to RE via stimulation of the sciatic nerve in vivo. Stimulated and control muscles were obtained at various time points post-RE and analyzed via Western blot and RT-PCR. A single bout of RE increased intracellular signaling (i.e., phosphorylations) and expression of mRNAs for insulin-like growth factor-I system components and myogenic markers (e.g., cyclin D1, myogenin). A rest interval of 48 h between RE bouts resulted in much greater summation of myogenic responses than 24- or 8-h rest intervals. This experimental approach should be useful for studying the regulatory mechanisms that control the hypertrophy response. These methods could also be used to compare and contrast different exercise parameters (e.g., concentric vs. eccentric, etc.).

The effects of accentuated eccentric loading on strength, muscle hypertrophy, and neural adaptations in trained individuals. Brandenburg JP, Docherty D. School of Physical Education, University of Victoria, Victoria, BC. The purpose of this study was to compare the strength and neuromuscular adaptations for dynamic constant external resistance (DCER) training and dynamic accentuated external resistance (DAER) training (resistance training employing an accentuated load during eccentric actions). Male subjects active in resistance training were assigned to either a DCER training group (n = 10) or a DAER training group (n = 8) for 9 weeks. Subjects in the DCER group performed 4 sets of 10 repetitions with a load of 75% concentric 1 repetition maximum (RM). Subjects in the DAER group performed 3 sets of 10 repetitions with a concentric load of 75% of 1RM and an eccentric load of approximately 120% of concentric 1RM. Three measures reflecting adaptation of elbow flexors and extensors were recorded pretraining and posttraining: concentric 1RM, muscle cross-sectional area (CSA), and specific tension. Strength was assessed at midtraining periods. No significant changes in muscle CSA were observed in either group. Both training groups experienced significant increases in concentric 1RM and specific tension of both the elbow flexors and extensors, but compared with DCER training, DAER training produced significantly greater increases in concentric 1RM of the elbow extensors. These

results suggest that, for some exercises, DAER training may be more effective than DCER training in developing strength within a 9-week training phase. However, for trained subjects, neither protocol is effective in eliciting muscle hypertrophy.

Acute muscle damage as a stimulus for training-induced gains in strength. Folland JP, Chong J, Copeman EM, Jones DA. Chelsea School Research Centre, University of Brighton, Eastbourne, United Kingdom. [email protected] PURPOSE: The purpose of this study was to investigate the effect of a single acute bout of maximal eccentric work upon the strength gains during 9 subsequent weeks of strength training. Eccentric work causes acute muscle damage that may initiate compensatory hypertrophy and enhance training-induced gains in strength. METHODS: Twenty-six healthy adults (21 +/- 1 yr, 7 women) trained the elbow flexors 3 d per week for 9 wk. One arm (C) performed purely conventional isotonic training, i.e., lifting and lowering. The other arm (E) began with a single bout of maximal eccentric work but thereafter undertook identical isotonic training. Every week dynamic lifting strength (1 RM) and isometric strength were measured. RESULTS: The results indicated that an acute bout of eccentric muscle damage does not accentuate training-induced gains in strength. Isometric strength of arm E fell by 15 +/- 2% (mean +/- SEM) 2 d after the bout of eccentric work, and, 4 d afterward, plasma creatine kinase levels were 1502 +/- 397 IU.L-1. Although arm E displayed rapid gains in strength from 2 d after the bout of eccentric work, these were not sustained, and for several weeks arm E showed significantly smaller gains in strength than arm C (isometric strength, 2 wk; dynamic lifting strength, 5 wk). CONCLUSIONS: After 9 wk of training, the gains in both isometric and dynamic lifting strength were similar for the two arms. A single bout of damaging eccentric work did not enhance the response to conventional strength training and significantly compromised strength gains for several weeks.

Mechanical load increases muscle IGF-I and androgen receptor mRNA concentrations in humans. Bamman MM, Shipp JR, Jiang J, Gower BA, Hunter GR, Goodman A, McLafferty CL Jr, Urban RJ. Department of Human Studies, University of Alabama at Birmingham, Birmingham, AL 35294, USA. [email protected] The mechanism(s) of load-induced muscle hypertrophy is as yet unclear, but increasing evidence suggests a role for locally expressed insulin-like growth factor I (IGF-I). We investigated the effects of concentric (CON) vs. eccentric (ECC) loading on muscle IGF-I mRNA concentration. We hypothesized a greater IGF-I response after ECC compared with CON. Ten healthy subjects (24.4 +/- 0.7 yr, 174.5 +/- 2.6 cm, 70.9 +/- 4.3 kg) completed eight sets of eight CON or ECC squats separated by 6-10 days. IGF-I, IGF binding protein-4 (IGFBP-4), and androgen receptor (AR) mRNA concentrations were determined in vastus lateralis muscle by RT-PCR before and 48 h after ECC and CON. Serum total testosterone (TT) and IGF-I were measured serially across 48 h, and serum creatine kinase activity (CK), isometric maximum voluntary contraction (MVC), and soreness were determined at 48 h. IGF-I mRNA concentration increased 62% and IGFBP-4 mRNA concentration decreased 57% after ECC (P < 0.05). Changes after CON were similar but not significant (P = 0.06-0.12). AR mRNA concentration increased (P < 0.05) after ECC (63%) and CON (102%). Serum TT and IGF-I showed little change. MVC fell 10% and CK rose 183%

after ECC (P < 0.05). Perceived soreness was higher (P < 0.01) after ECC compared with CON. Results indicate that a single bout of mechanical loading in humans alters activity of the muscle IGF-I system, and the enhanced response to ECC suggests that IGF-I may somehow modulate tissue regeneration after mechanical damage.

Changes in muscle strength, muscle fibre size and myofibrillar gene expression after immobilization and retraining in humans. Hortob�gyi T, Dempsey L, Fraser D, Zheng D, Hamilton G, Lambert J, Dohm L. Biomechanics Laboratory and Departments of Biochemistry and Physical Therapy, East Carolina University, Greenville, NC 27858, USA. [email protected] 1. Changes in muscle strength, vastus lateralis fibre characteristics and myosin heavy-chain (MyoHC) gene expression were examined in 48 men and women following 3 weeks of knee immobilization and after 12 weeks of retraining with 1866 eccentric, concentric or mixed contractions. 2. Immobilization reduced eccentric, concentric and isometric strength by 47 %. After 2 weeks of spontaneous recovery there still was an average strength deficit of 11 %. With eccentric and mixed compared with concentric retraining the rate of strength recovery was faster and the eccentric and isometric strength gains greater. 3. Immobilization reduced type I, IIa and IIx muscle fibre areas by 13, 10 and 10 %, respectively and after 2 weeks of spontaneous recovery from immobilization these fibres were 5 % smaller than at baseline. Hypertrophy of type I, IIa and IIx fibres relative to baseline was 10, 16 and 16 % after eccentric and 11, 9 and 10 % after mixed training (all P < 0.05), exceeding the 4, 5 and 5 % gains after concentric training. Type IIa and IIx fibre enlargements were greatest after eccentric training. 4. Total RNA/wet muscle weight and ty I, IIa and IIx MyoHC mRNA levels did not change differently after immobilization and retraining. Immobilization downregulated the expression of type I MyoHC mRNA to 0.72-fold of baseline and exercise training upregulated it to 0.95 of baseline. No changes occurred in type IIa MyoHC mRNA. Immobilization and exercise training upregulated type IIx MyoHC mRNA 2.9-fold and 1.2-fold, respectively. For the immobilization segment, type I, IIa and IIx fibre area and type I, IIa and IIx MyoHC mRNA correlated (r = 0.66, r = 0.07 and r = -0.71, respectively). 5. The present data underscore the role muscle lengthening plays in human neuromuscular function and adaptation. Nuclear magnetic resonance evidence of different muscular adaptations after resistance training. Walker PM, Brunotte F, Rouhier-Marcer I, Cottin Y, Casillas JM, Gras P, Didier JP. Service de Spectroscopie RMN et M�decine Nucl�aire, Centre Hospitalier Universitaire de Dijon, France. OBJECTIVE: To evaluate muscle bioenergetics, muscle cross-sectional area (CSA), and soreness when the gastrocnemius was subjected to concentric and concentric/eccentric resistance training modes. DESIGN: Prospective study, before and after training. The subjects served as their own controls. SETTING: Rehabilitation center and nuclear magnetic resonance spectroscopy unit of a university hospital. PARTICIPANTS: Sixteen healthy young volunteers from the local physiotherapist school. INTERVENTION: Two distinct resistive training programs were evaluated on the gastrocnemius: a protocol consisting of concentric contractions only and a mixed concentric/eccentric program. MAIN OUTCOME MEASURES: Maximal isometric resistance was measured after each training session. Before and after training, muscle CSA was appreciated using magnetic resonance imaging,

whereas changes in muscle pH, phosphorus metabolite ratios, maximal oxidative power (Pmax), and oxidative phosphorylation were studied using 31P nuclear magnetic resonance spectroscopy at rest and during an incremental exercise protocol. RESULTS: Magnetic resonance imaging revealed a significant increase (7.1%) in the gastrocnemius CSA in the concentric-eccentric group only. The PCr/Pi (8.3 +/- 0.9 vs 10.4 +/- 1.7) and PCr/ATP (3.68 +/- .36 vs 4.07 +/- .27) resting ratios increased significantly (p = .008) after concentric-eccentric resistance training. Pmax was significantly improved in the concentric-eccentric group (7.0 +/- 2.1W vs 8.4 +/- 1.8W: p < .02). This mixed protocol also reduced the incidence of muscular soreness. CONCLUSION: The data suggest that the improved oxidative mechanical power output could be due mainly to a greater muscle cross-section in the concentric-eccentric group, with circumstantial evidence suggesting a relatively higher type IIa fiber activity.

Effects of concentric and eccentric training on muscle strength, cross-sectional area, and neural activation. Higbie EJ, Cureton KJ, Warren GL 3rd, Prior BM. Department of Exercise Science, University of Georgia, Athens 30602-3654, USA. We compared the effects of concentric (Con) and eccentric (Ecc) isokinetic training on quadriceps muscle strength, cross-sectional area, and neural activation. Women (age 20.0 +/- 0.5 yr) randomly assigned to Con training (CTG; n = 16), Ecc training (ETG; n = 19), and control (CG; n = 19) groups were tested before and after 10 wk of unilateral Con or Ecc knee-extension training. Average torque measured during Con and Ecc maximal voluntary knee extensions increased 18.4 and 12.8% for CTG, 6.8 and 36.2% for ETG, and 4.7 and -1.7% for CG, respectively. Increases by CTG and ETG were greater than for CG (P < 0.05). For CTG, the increase was greater when measured with Con than with Ecc testing. For ETG, the increase was greater when measured with Ecc than with Con testing. The increase by ETG with Ecc testing was greater than the increase by CTG with Con testing. Corresponding changes in the integrated voltage from an electromyogram measured during strength testing were 21.7 and 20.0% for CTG, 7.1 and 16.7% for ETG, and -8.0 and -9.1% for CG. Quadriceps cross-sectional area measured by magnetic resonance imaging (sum of 7 slices) increased more in ETG (6.6%) than in CTG (5.0%) (P < 0.05). We conclude that Ecc is more effective than Con isokinetic training for developing strength in Ecc isokinetic muscle actions and that Con is more effective than Ecc isokinetic training for developing strength in Con isokinetic muscle actions. Gains in strength consequent to Con and Ecc training are highly dependent on the muscle action used for training and testing. Muscle hypertrophy and neural adaptations contribute to strength increases consequent to both Con and Ecc training.

Adaptive responses to muscle lengthening and shortening in humans. Hortob�gyi T, Hill JP, Houmard JA, Fraser DD, Lambert NJ, Israel RG. Biomechanics Laboratory and Department of Medicine and Physical Therapy, East Carolina University, Greenville, North Carolina 27858, USA. We tested the hypothesis that exercise training with maximal eccentric (lengthening) muscle actions results in greater gains in muscle strength and size than training with concentric (shortening) actions. Changes in muscle strength, muscle fiber size, and surface electromyographic (EMG) activity of the quadriceps

muscle were compared after 36 sessions of isokinetic concentric (n = 8) or eccentric (n = 7) exercise training over 12 wk with use of a one-leg model. Eccentric training increased eccentric strength 3.5 times more (pre/post 46%, P < 0.05) than concentric training increased concentric strength (pre/post 13%). Eccentric training increased concentric strength and concentric training increased eccentric strength by about the same magnitude (5 and 10%, respectively, P > 0.05). Eccentric training increased EMG activity seven times more during eccentric testing (pre/post 86%, P < 0.05) than concentric training increased EMG activity during concentric testing (pre/post 12%). Eccentric training increased the EMG activity measured during concentric tests and concentric training increased the EMG activity measured during eccentric tests by about the same magnitude (8 and 11%, respectively, P > 0.05). Type I muscle fiber percentages did not change significantly, but type IIa fibers increased and type IIb fibers decreased significantly (P < 0.05) in both training groups. Type I fiber areas did not change significantly (P > 0.05), but type II fiber area increased approximately 10 times more (P < 0.05) in the eccentric than in the concentric group. It is concluded that adaptations to training with maximal eccentric contractions are specific to eccentric muscle actions that are associated with greater neural adaptation and muscle hypertrophy than concentric exercise.