AIM:The predictions of scaling of skeletal muscle shortening velocity made by A.V. Hill 60-years ago have proven to be remarkably accurate at the cellular level. The current investigation looks to extend the study of scaling of contractile speed to the level of the molecular motor protein myosin at both physiological and unphysiological low temperatures.METHODS:A single muscle cell in vitro motility assay to test myosin function, i.e. myosin extracted from short single muscle fibre segments, was used in four species representing a 5 500-fold difference in body mass (rat, man, horse and rhinoceros) at temperatures ranging from 15 to 35 °C.RESULTS:The in vitro motility speed increased as the temperature of the assay increased, but a more profound effect was observed on the slower isoforms, narrowing the relative differences between fast and slow myosin heavy chain (MyHC) isoforms at physiological temperature in all species. The in vitro motility speed varied according to MyHC isoform within each species: I < IIa < IIx < IIb, but the expected scaling relationship within orthologous myosin isoforms was not observed at any temperature.CONCLUSION:The scaling effect of body size and limb length on shortening velocity at the muscle fibre level, i.e. the decreasing shortening velocity associated with increasing body weight and limb length, was not confirmed at the motor protein level when including mammals of very large size. Thus, other factors than myosin structure and function appear to cause this scaling effect and thin filament isoform expression or myofilament lattice spacing are forwarded as alternative underlying factors.

AIM The mechanism linking exercise intensity to the magnitude of the immune response is not completely understood. The purpose of this investigation was to determine whether the immune response to resistance exercise was associated with (1) changes in workload or (2) anaerobic exercise intensity. METHODS Previously untrained women underwent 6 months of resistance training for lower and upper body (TOTAL, n = 34) or for upper body alone (UPPER, n = 30). Lymphocyte subsets [T (CD3+), CD4+, CD8+, NK and B], functional markers (CD45RA+ and CD45RO+), and mitogen (phytohemagglutinin-M, concanavalin A and pokeweed mitogen) and superantigen (staphylococcus a. cowans)-stimulated proliferation were measured from blood samples collected pre- and post-exercise for a squat resistance exercise consisting of six sets of 10 repetitions at 75% of one repetition maximum. This protocol was performed before (T0) and after 3 (T3) and 6 months (T6) of training. RESULTS Lymphocyte recruitment to the circulation and proliferation following resistance exercise did not differ between training groups at any time, although the TOTAL group performed at a higher workload as training progressed. With respect to anaerobic intensity, exercise-induced increases in NK, CD4+, CD8+ and B lymphocyte concentrations were 42 (P = 0.07), 76 (P < 0.05), 72 (P < 0.05) and 242% (P < 0.01) greater in women in the highest compared with the lowest post-exercise lactate quartiles. Lymphocyte proliferation did not differ between lactate quartiles. CONCLUSIONS Anaerobic intensity, rather than increased strength and workload, is associated with the number of lymphocytes recruited to the circulation, but not T and B cell proliferation responses.

INTRODUCTION Over 50 years ago, A. V. Hill hypothesized that skeletal muscle shortening velocity would scale with body size. This means that skeletal muscle shortening velocity would be inversely related to an animal's body size. This relationship has been confirmed in the type I fibers, but little work has been done examining the effects of scaling on the fast, type IIA fibers. The purpose of this study is to examine the effect of body size on skeletal muscle shortening velocity in type I and IIA muscle fibers at the cellular level. METHODS Muscle tissue was obtained in six species; mouse, rat, dog, human, horse and rhinoceros. Single fiber shortening velocity was measured using the slack test. Myosin heavy chain composition for each fiber was determined by gel electrophoresis. Scaling coefficients were determined from the plot of the log of the shortening velocity or in vitro motility speed vs. the log of the body mass. RESULTS There was nearly a three-fold difference in shortening velocity between the smallest and largest species for type I fibers and nearly two-fold difference in type IIA fibers. The scaling coefficients for shortening velocity were-0.09 for type I fibers and −0.04 for type IIA fibers. Interestingly, both the type I and IIA human fibers were slower than would be predicted by the relationship predicted by the other species. CONCLUSIONS The effects of body size on skeletal muscle shortening velocity were present in both fast and slow twitch fibers. The observation that the shortening velocity of the human fibers did not correspond with the other species may be related to the gait and postural characteristics of the various species compared with humans (quadripedal vs. bipedal).

The purpose of this investigation was to determine the influence of physical strength and the ability to do more total work on human growth hormone (GH) variants to a heavy resistance exercise protocol in untrained women. From a distribution of 100 healthy, untrained women, the strongest 10 women (S) and the weakest 10 women (W) were compared for GH responses pre- and post an acute heavy resistance exercise test (AHRET, 6 sets of 10 RM squats, 2 minutes rest between sets). Blood samples were obtained pre-exercise and immediately post-exercise and subsequently analysed in total as well as fractionated by Sephacryl S-100R column chromatography into three molecular weight size classes: fraction A: > 60 kD, fraction B: 30-60 kD, fraction C: < 30 kD. For each total sample as well as each fraction, immunoreactive GH was measured via the Nichols IRMA, while bioactive GH was measured via the hypox rat tibial line bioassay and Diagnostic Systems Laboratory's immunofunctional GH ELISA. No exercise-induced changes or differences between groups were observed in the tibial line bioassay. However, the S group displayed a significantly higher pre-exercise resting value in the total fraction than the W group. Conversely, the W group exhibited a significantly higher pre-exercise value in the smaller molecular weight fraction C. With regards to the immunofunctional and immunoreactive assays, the total fraction, fraction A, and fraction B demonstrated significant (P < or = 0.05) exercise-induced increases in both the S and W group despite no group differences. For the Nichols and immunofunctional assays significant exercise-induced changes were observed in the smaller molecular weight C fraction in the W group but not the S group. However, the S group displayed a significantly higher pre-exercise value in fraction C relative to the W group. These data demonstrate for the first time that differences exist in the GH molecular weight variants between strong and weak untrained women, with the lower molecular weight variants seemingly less responsive to greater amounts of exercise in stronger women, thus suggesting differential regulation of GH molecular weight variants during resistance exercise due to pre-existing physical parameters.

The aim of this study was to further investigate the mechanism of suppression of natural killer (NK) cell cytotoxic activity in peripheral blood following strenuous exercise. Blood was collected for analysis of NK cell concentration, cytotoxic activity, CD2 surface expression and perforin gene expression from runners (RUN, n=6) and resting controls (CONTROL, n=4) pre-exercise, 0, 1.5, 5, and 24 h following a 60-min treadmill run at 80% of VO2 peak. Natural killer cytotoxic activity, measured using a whole blood chromium release assay, fluctuated minimally in the CONTROL group and increased by 63% and decreased by 43% 0 and 1.5 h post-exercise, respectively, in the RUN group (group x time, P < 0.001). Lytic index (cytotoxic activity per cell) did not change. Perforin mRNA, measured using quantitative real-time polymerase chain reaction (QRT-PCR) decreased from pre- to post-exercise and remained decreased through 24 h. The decrease from pre- to 0 h post-exercise was seen predominately in the RUN group and was inversely correlated (r=- 0.95) to pre-exercise perforin mRNA. The NK cell surface expression of CD2 (lymphocyte function-associated antigen-2) was determined using fluorescent antibodies and flow cytometry. There was no change in the proportion of NK cells expressing CD2 or CD2 density. We conclude that (1) numerical redistribution accounted for most of the change in NK cytotoxic activity following a strenuous run, (2) decrease in perforin gene expression during the run was inversely related to pre-exercise levels but did not parallel changes in cytotoxic activity, and (3) CD2 surface expression was not affected by exercise.

PURPOSEThe effects of resistance training programs on strength, power, and military occupational task performances in women were examined.METHODSUntrained women aged (mean +/- SD) 23 +/- 4 yr were matched and randomly placed in total- (TP, N = 17 and TH, N = 18) or upper-body resistance training (UP, N = 18 and UH, N = 15), field (FLD, N = 14), or aerobic training groups (AER, N = 11). Two periodized resistance training programs (with supplemental aerobic training) emphasized explosive exercise movements using 3- to 8-RM training loads (TP, UP), whereas the other two emphasized slower exercise movements using 8- to 12-RM loads (TH, UH). The FLD group performed plyometric and partner exercises. Subjects were tested for body composition, strength, power, endurance, maximal and repetitive box lift, 2-mile loaded run, and U.S. Army Physical Fitness Tests before (T0) and after 3 (T3) and 6 months of training (T6). For comparison, untrained men (N = 100) (MEN) were tested once.RESULTSSpecific training programs resulted in significant increases in body mass (TP), 1-RM squat (TP, TH, FLD), bench press (all except AER), high pull (TP), squat jump (TP, TH, FLD), bench throw (all except AER), squat endurance (all except AER), 1-RM box lift (all except aerobic), repetitive box lift (all), push-ups (all except AER), sit-ups (all except AER), and 2-mile run (all).CONCLUSIONSStrength training improved physical performances of women over 6 months and adaptations in strength, power, and endurance were specific to the subtle differences (e.g., exercise choice and speeds of exercise movement) in the resistance training programs (strength/power vs strength/hypertrophy). Upper- and total-body resistance training resulted in similar improvements in occupational task performances, especially in tasks that involved upper-body musculature. Finally, gender differences in physical performance measures were reduced after resistance training in women, which underscores the importance of such training for physically demanding occupations.

Regional fat distribution (RFD) has been associated with metabolic derangements in populations with obesity. For example, upper body fat patterning is associated with higher levels of free testosterone (FT) and lower levels of sex-hormone binding globulin (SHBG). We sought to determine the extent to which this relationship was true in a healthy (i.e., non-obese) female population and whether RFD influenced androgen responses to resistance exercise. This study examined the effects of RFD on total testosterone (TT), FT, and SHBG responses to an acute resistance exercise test (ARET) among 47 women (22+/-3 years; 165+/-6 cm; 62+/-8 kg; 25+/-5%BF; 23+/-3 BMI). RFD was characterized by 3 separate indices: waist-to-hip ratio (WHR), ratio of upper arm fat to mid-thigh fat assessed with magnetic resonance imaging (MRI ratio), and ratio of subscapular to triceps ratio (SB/TRi ratio). Skinfolds were measured for the triceps, chest, subscapular, mid-axillary, suprailaic, abdomen, and thigh regions. The ARET consisted of 6 sets of 10 RM squats separated by 2-min rest periods. Blood was obtained pre- and post- ARET. TT, FT, and SHBG concentrations were determined by radioimmunoassay. Subjects were divided into tertiles from the indices of RFD, and statistical analyses were performed by an ANOVA with repeated measures (RFD and exercise as main effects). Significant (p < or = .05) increases following the AHRET were observed for TT (approximately 25%), FT (approximately 25%), and SHBG (4%). With multiple regression analysis, anthropometric measures significantly predicted pre- concentrations of FT, post-concentrations of TT, and pre-concentrations of SHBG. The SB/TRi and MRI ratios but not the WHR, were discriminant for hormonal concentrations among the tertiles. In young, healthy women, resistance exercise can induce transient increases in testosterone, and anthropometric markers of adiposity correlate with testosterone concentrations.

Rodent motor units, muscle fibers, and motor proteins undergo significant aging-related changes. Such changes include spatial organization and physiological properties of fast- and slow-twitch single motor units, regulation of contractile speed and force generation capacity at the muscle fiber level, and altered functional properties of the motor protein myosin. In addition to specific changes, there also appears to be a "disorganization" of the coordinated expression of contractile, sarcoplasmic reticular, and mitochondrial protein isoforms in aging skeletal muscle. This is suggested to have a strong impact on aging-related impairments in muscle function in addition to the changes in specific muscle proteins.

A decrease in specific tension (SpT), or force per unit cross-sectional area of skeletal muscle, in the elderly is well documented. This decrease may be due to a decrease in the number of acto-myosin interactions, a decrease in the force per acto-myosin interaction, or a combination of both of these. We hypothesized that a decrease in the concentration of the contractile proteins would be, at least in part, responsible for the decrease in SpT observed in the elderly. To test this hypothesis, the actin and myosin heavy chain (MyHC) concentration was determined from 73 single muscle fibers from a group of young men (18–25 years) and 72 muscle fibers from old men (65–80 years). The volume of fluorescent-labeled single muscle fibers was measured using confocal microscopy and the contractile protein content was determined using SDS-PAGE with Commassie Blue staining and soft laser densitometry. The main findings of the study were as follows: 1) An aging-related decrease in muscle fiber cross-sectional area, affecting primarily muscle fibers expressing fast MyHC isoforms (Young: 4,695 ± 170μm2 vs. Old: 4,332 ± 124 μm2); 2) A significant aging-related loss of MyHC, but not actin, per unit of cell volume (MyHC: Young: 95.6 ± 4.6 O. D. units vs. Old: 87.2 ± 5.3 O. D. units). There were no differences detected in actin concentration. These data demonstrate that the decrease in SpT in the elderly is, at least in part due to a decrease in the concentration of the molecular motor protein, myosin.

The purpose of this study was to determine the impact of an oral contraceptive on growth hormone(GH) forms following heavy resistance exercise. Two groups of healthy women: an oral contraceptive group (OC) (n = 24, 23.5 ± 0.65yrs, 63.2 ± 1.6kg, 165.4 ± 1.6cm, 24.8 ± 1.2% fat) and a normally menstruating group (NM) in the early follicular phase (n = 35, 23.5 ± 0.78yrs, 65.6 ± 1.7kg, 165.8 ± 1.0cm, 25.7 ± 0.98% fat) volunteered. Blood was collected before and after 6 sets of 10RM with 2 min rest between sets in the squat exercise. Plasma was fractionated by size exclusion chromatography into 3 size classes; viz. > 60 kD (fr A); 30 to 60 kD (fr. B) and < 30 kD (fr. C) prior to GH assays. GH concentrations in these fractions, as well as in unfractioned plasma and GSH treated samples were measured by immunoradiometric assay, polyclonal competitive RIA, immunofunctional (IF) assay, and rat tibial bioassay. Significant (p < 0.05) increases in all GH fractions were observed post-exercise in both groups for all assays except for the tibial line assay and for IF-GSH fr. A in the NM group. In general OC group had significantly higher values for GH in total as well as fractioned A and B samples. In fr. C no differences were observed between the groups. These data indicate that an oral contraceptive can influence the magnitude of some immediate post-exercise GH responses to heavy resistance exercise, but these differences are not consistent across all molecular forms of the GH family of polypeptides. Supported in part by US Army Women's Health grant (17 95-C-5069) to wjk

This study examined the hypothesis that exercise-induced changes in circulating testosterone would be centrally mediated via hypothalamic-pituitary release of luteinizing hormone (LH). We tested this hypothesis by examining overnight LH, total and free testosterone (TT and FT), and cortisol (C) concentrations in 10 young healthy men (21 +/- 1 yr) during two experimental sessions: a control and an acute heavy-resistance exercise bout (50 total sets consisting of squats, bench press, leg press, and latissimus dorsi pull-down). Exercise was performed from 1500 to 1700, and blood sampling began at 1700 and continued until 0600 the next morning. Blood was sampled every 10 min for LH and every hour for TT, FT, and C. Hormonal concentrations were determined via RIA, and the secretion characteristics of LH were analyzed with deconvolution analysis. When overnight postexercise concentrations were compared with control concentrations, no statistically significant (P < or = 0.05) differences were observed for LH half-life, LH pulse frequency, interpulse interval, pulse amplitude, or pulse mass. Significant differences were observed for LH production rate (13.6 +/- 4 and 17.9 +/- 5 IU. l distribution volume(-1) x day(-1) for exercise and control, respectively, a 24% reduction). For the ANOVA marginal main effect means due to condition, C was significantly elevated (5.9 +/- 0.7 vs. 4.0 +/- 0.4 microg/dl), while TT (464 +/- 23 vs. 529 +/- 32 ng/dl) and FT (15.6 +/- 0.7 vs. 18.3 +/- 0.9 pg/ml) were significantly decreased for the exercise condition. These data demonstrate that the decline in overnight testosterone concentrations after acute heavy-resistance exercise is accompanied by a blunted LH production rate and elevated C concentrations.

PURPOSE:The purpose of this investigation was to determine the long-term training adaptations associated with low-volume circuit-type versus periodized high-volume resistance training programs in women.METHODS:34 healthy, untrained women were randomly placed into one of the following groups: low-volume, single-set circuit (SSC; N = 12); periodized high-volume multiple-set (MS; N = 12); or nonexercising control (CON) group (N = 10). The SSC group performed one set of 8-12 repetitions to muscular failure 3 d x wk(-1). The MS group performed two to four sets of 3-15 repetitions with periodized volume and intensity 4 d x wk(-1). Muscular strength, power, speed, endurance, anthropometry, and resting hormonal concentrations were determined pretraining (T1), after 12 wk (T2), and after 24 wk of training (T3).RESULTS:1-RM bench press and leg press, and upper and lower body local muscular endurance increased significantly (P < or = 0.05) at T2 for both groups, but only MS showed a significant increase at T3. Muscular power and speed increased significantly at T2 and T3 only for MS. Increases in testosterone were observed for both groups at T2 but only MS showed a significant increase at T3. Cortisol decreased from T1 to T2 and from T2 to T3 in MS. Insulin-like growth factor-1 increased significantly at T3 for SSC and at T2 and T3 for MS. No changes were observed for growth hormone in any of the training groups.CONCLUSION:Significant improvements in muscular performance may be attained with either a low-volume single-set program or a high-volume, periodized multiple-set program during the first 12 wk of training in untrained women. However, dramatically different training adaptations are associated with specific domains of training program design which contrast in speed of movement, exercise choices and use of variation (periodization) in the intensity and volume of exercise.

The effects of exercise on the molecular nature of secreted human growth hormone (GH) or its biological activity are not well understood. Plasma from women (average age 23.6 yr, n = 35), drawn before and after an acute heavy resistance exercise test, was fractionated by size exclusion chromatography into three size classes, namely, > 60 kDa (fraction A), 30-60 kDa (fraction B), and < 30 kDa (fraction C), before GH assay. Concentrations of GH in these fractions, as well as in unfractioned plasma, were measured by the Nichols immunoradiometric assay, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) polyclonal competitive RIA, Diagnostic Systems Laboratory's immunofunctional assay (measures dimerization-capable species), and the rat tibial bioassay. Significantly increased circulating GH concentrations of two- to fourfold were observed when immunoassays in unfractionated plasma samples were used, but they showed no significant change with use of the rat tibial bioassay. Significant exercise-induced increases in GH were found in fractions B and C but not in fraction A. Because chemical reduction of the samples before GH immunoassay significantly increased GH concentrations in fractions B and C (Nichols and NIDDK kits) after exercise, it is concluded that exercise may specifically increase release of disulfide-linked hormone molecules and/or fragments. Finally, because most of the GH released after exercise was able to dimerize the GH receptor in vitro, it is also concluded that these forms have the two intact binding sites required to initiate signal transduction in target cells.

This study evaluated the individual components of the insulin-like growth factor I (IGF-I) system [i.e., total and free IGF-I, insulin-like growth factor binding protein (IGFBP)-2 and -3, and the acid-labile subunit (ALS)] in 10 young, healthy men (age: 22 +/- 1 yr, height: 177 +/- 2 cm, weight: 79 +/- 3 kg, body fat: 11 +/- 1%) overnight for 13 h after two conditions: a resting control (Con) and an acute, heavy-resistance exercise protocol (Ex). The Ex was a high-volume, multiset exercise protocol that alternated between 10- and 5-repetition maximum sets with 90-s rest periods between sets. The Ex was performed from 1500 to 1700; blood was obtained immediately postexercise and sampled throughout the night (every 10 min for the first hour and every hour thereafter) until 0600 the next morning. For the first hour, significant differences (P < or = 0.05) were only observed for IGFBP-3 (Ex: 3,801 > Con: 3,531 ng/ml). For the overnight responses, no differences were observed for total or free IGF-I or IGFBP-3, whereas IGFBP-2 increased (Ex: 561 > Con: 500 ng/ml) and ALS decreased (Ex: 35 < Con: 39 microg/ml) after exercise. The results from this study suggest that the impact that resistance exercise exerts on the circulating IGF-I system is not in the alteration of the amount of IGF-I but rather of the manner in which IGF-I is partitioned among its family of binding proteins. Thus acute, heavy-resistance exercise can lead to alterations in the IGF-I system that can be detected in the systemic circulation.

Resistance training, by virtue of an increase in muscle mass and the predominately anaerobic nature of the metabolic stress, is likely to influence the immune system differently than endurance training. The aim of this study was to determine whether resistance training influences blood-borne lymphocytes. Previously untrained women underwent one of six training programs or were non-training controls (CON, n = 7). Five of the programs involved resistance training: total body power (TBP, n = 16) and hypertrophy (TBH, n = 17), upper body power (UBP, n = 20) and hypertrophy (UBH, n = 18), or field-based ballistics and partner-resistance exercise (FLD, N = 15). The remaining program was predominately aerobic exercise (AER, n = 11). Resting immune function was evaluated from a fasting morning blood sample in Sep/Oct (0 mo.), Nov/Dec (3 mo.) and Apr/May (6 mo.). Leukocyte differentials, lymphocyte subsets and functional markers, and mitogen-stimulated lymphocyte proliferation were measured. A significant group × time interaction (P < 0.05) was detected for NK lymphocyte concentration. Mean group increases ranged from 18.5 to 38% at 3 months for TBP, UBP, TBH, and UBH groups; −9.4 to −12.5% for the AER, FLD, and CON groups. These changes did not persist through 6 months of training. The CD8+ fraction of NK cells made up the majority of this increase. T lymphocytes broken down by CD4+, CD8+, L-selectin+, very late antigen-4+, naive, and memory subsets did not change amongst groups or across time. The lymphocyte proliferation response varied depending on the mitogen and concentration used for stimulation (phytohemagglutinin-M, concanavalin A, pokeweed mitogen, and staphylococcus a. cowans at sub-optimal and optimal concentrations). For these mitogens, generally, there was little fluctuation in the resistance trained and CON groups, while AER and FLD groups decreased over time. Thus, there may be a mode-specific influence of resistance training on NK cell distibution and some lymphocyte functions. Supported by DOD grant US Army #DAMD 17-95-C-5069 to WJK.