Flexor bias of joint position in humans during spaceflight.

The ability to estimate ankle and elbow joint position was tested before, during, and after a 17-day spaceflight. Subjects estimated targeted joint angles during isovelocity (IsoV) joint movements with agonist muscle groups either active or relaxed. These movements included elbow extension (EE) and elbow flexion (EF), and plantarflexion (PF) and dorsiflexion (DF) of the ankle. Subjects also estimated these joint positions while moving the dynamometer at their chosen (variable) velocity (VarV) during EE and PF. For IsoV tests, no differences were observed between active and passive movements for either the ankle or elbow. Compared with those of pre-flight test days, estimates of targeted elbow joint angles were approximately 5 degrees to 15 degrees more flexed in-flight, and returned toward the pre-flight values during recovery. The spaceflight effects for the ankle were inconsistent and less prevalent than those for the elbow. The VarV PF test condition for the 120 degrees target angle at the ankle exhibited approximately 5 degrees to 7 degrees more DF target angle estimates in-flight compared with those pre- or post-flight. In contrast, during IsoV PF there was a tendency for ankle estimates to be approximately 2 degrees to 3 degrees more PF after 2-3 days exposure to spaceflight. These data indicate that during spaceflight the perception of elbow extension is greater than actuality, and are consistent with the interpretation that microgravity induced a flexor bias in the estimation of the actual elbow joint position. Moreover, these effects in joint proprioception during spaceflight were observed in individual isolated single-joint movements during tasks in which vestibular function in maintaining posture were minimal.

Transcriptional regulation of IGF-I expression in skeletal muscle.

The present study investigated the role of transcription in the regulation of insulin-like growth factor (IGF)-I expression in skeletal muscle. RT-PCR was used to determine endogenous expression of IGF-I pre-mRNA and mRNA in control (Con) and functionally overloaded (FO) rat plantaris. The transcriptional activities of five different-length IGF-I promoter fragments controlling transcription of a firefly luciferase (FLuc) reporter gene were tested in vitro by transfection of myoblasts or in vivo during FO by direct gene transfer into the plantaris. Increased endogenous IGF-I gene transcription during 7 days of plantaris FO was evidenced by an approximately 140-160% increase (P < 0.0001) in IGF-I pre-mRNA (a transcriptional marker). IGF-I mRNA expression also increased by approximately 90% (P < 0.0001), and it was correlated (R = 0.93; P < 0.0001) with the pre-mRNA increases. The three longest IGF-I exon 1 promoters induced reporter gene expression in proliferating C2C12 and L6E9 myoblasts. In differentiated L6E9 myotubes, promoter activity increased approximately two- to threefold over myoblasts. Overexpression of calcineurin and MyoD increased the activity of the -852/+192 promoter in C2C12 myotubes by approximately 5- and approximately 18-fold, respectively. However, FO did not induce these exogenous promoter fragments. Nevertheless, the present findings are consistent with the hypothesis that the IGF-I gene is transcriptionally regulated during muscle hypertrophy in vivo as evidenced by the induction of the endogenous IGF-I pre-mRNA during plantaris FO. The exon 1 promoter region of the IGF-I gene is sufficient to direct inducible expression in vitro; however, an in vivo response to FO may require elements outside the -852/+346 region of the exon 1 IGF-I promoter or features inherent to the endogenous IGF-I gene.

Muscle afferent-pituitary axis: a novel pathway for modulating the secretion of a pituitary growth factor.

Evidence is presented for a novel muscle-neuro-endocrine pathway for modulating the secretion of an unidentified pituitary growth factor by proprioceptive input from skeletal muscle afferents. Exercise stimulates the release of this growth factor, whereas chronic unloading associated with bed rest or spaceflight abrogates the normal exercise stimulus.

Sensorimotor adaptations to microgravity in humans.

Motor function is altered by microgravity, but little detail is available as to what these changes are and how changes in the individual components of the sensorimotor system affect the control of movement. Further, there is little information on whether the changes in motor performance reflect immediate or chronic adaptations to changing gravitational environments. To determine the effects of microgravity on the neural control properties of selected motor pools, four male astronauts from the NASA STS-78 mission performed motor tasks requiring the maintenance of either ankle dorsiflexor or plantarflexor torque. Torques of 10 or 50% of a maximal voluntary contraction (MVC) were requested of the subjects during 10 degrees peak-to-peak sinusoidal movements at 0.5 Hz. When 10% MVC of the plantarflexors was requested, the actual torques generated in-flight were similar to pre-flight values. Post-flight torques were higher than pre- and in-flight torques. The actual torques when 50% MVC was requested were higher in- and post-flight than pre-flight. Soleus (Sol) electromyographic (EMG) amplitudes during plantarflexion were higher in-flight than pre- or post-flight for both the 10 and 50% MVC tasks. No differences in medial gastrocnemius (MG) EMG amplitudes were observed for either the 10 or 50% MVC tasks. The EMG amplitudes of the tibialis anterior (TA), an antagonist to plantarflexion, were higher in- and post-flight than pre-flight for the 50% MVC task. During the dorsiflexion tasks, the torques generated in both the 10 and 50% MVC tasks did not differ pre-, in- and post-flight. TA EMG amplitudes were significantly higher in- than pre-flight for both the 10 or 50% MVC tasks, and remained elevated post-flight for the 50% MVC test. Both the Sol and MG EMG amplitudes were significantly higher in-flight than either pre- or post-flight for both the 10 and 50% MVC tests. These data suggest that the most consistent response to space flight was an elevation in the level of contractions of agonists and antagonists when attempting to maintain constant torques at a given level of MVC. Also, the chronic levels of EMG activity in selected ankle flexor and extensor muscles during space flight and during routine activities on Earth were recorded. Compared with pre- and post-flight values, there was a marked increase in the total EMG activity of the TA and the Sol and no change in the MG EMG activity in-flight. These data indicate that space flight, as occurs on shuttle missions, is a model of elevated activation of both flexor and extensor muscles, probably reflecting the effects of programmed work schedules in flight rather than a direct effect of microgravity.

Muscle afferent activity modulates bioassayable growth hormone in human plasma.

Immunoassayable and bioassayable growth hormone responses to vibration-induced activation of muscle spindle afferents of the soleus (Sol) or tibialis anterior (TA) muscles were studied in 10 men. Subjects were supine while a 10-min vibration stimulus (100 Hz; 1.5-mm amplitude) was applied to the muscle, with each of the muscles tested on separate days. Blood samples were collected before, during, immediately after, and after 5 and 10 min of vibration. Plasma growth hormone concentrations were determined by radioimmunoassay (IGH) for all sampling periods and by bioassay (BGH; measurement of tibial epiphysial cartilage growth in hypophysectomized rats) for samples obtained before and immediately after vibration. Plasma IGH concentrations were similar at all time points during the Sol or TA experiments. After 10 min of muscle vibration, mean plasma BGH was elevated 94% [1,216 +/- 148 (SD) to 2, 362 +/- 487 microg/l; P = 0.0001] for TA and decreased 22% (1,358 +/- 155 to 1,058 +/- 311 microg/l; P = 0.09) for Sol. These data demonstrate that activation of TA muscle spindle afferents increases circulating BGH but not IGH. The absence of a similar vibration-induced BGH response for the Sol indicates a differential regulation of BGH release by these two predominantly slow muscles, perhaps related to their respective flexor and extensor functions. These data indicate that a muscle afferent-pituitary axis modulates the release of BGH, but not IGH, from the pituitary in humans and that this axis is muscle specific, similar to that observed in rats.

Spaceflight suppresses exercise-induced release of bioassayable growth hormone.

We have reported that bed rest suppressed the release of bioassayable growth hormone (BGH) that normally occurs after an acute bout of unilateral plantar flexor exercise (G. E. McCall, C. Goulet, R. E. Grindeland, J. A. Hodgson, A. J. Bigbee, and V. R. Edgerton. J. Appl. Physiol. 83: 2086-2090, 1997). In the present study, the effects of spaceflight on the hormonal responses to this exercise protocol were examined. Four male astronauts on the National Aeronautics and Space Administration Shuttle Transport System (STS-78) mission completed the exercise protocol before, during, and after a 17-day spaceflight. The maximal voluntary contraction torque output at the onset of exercise was similar on all test days. Before spaceflight, plasma BGH increased 114-168% from pre- to postexercise. During spaceflight and after 2 days recovery at normal gravity (1 G), the BGH response to exercise was absent. After 4 days of recovery, this response was restored. Plasma concentrations of immunoassayable growth hormone were similar at all time points. The preexercise plasma immunoassayable insulin-like growth factor I (IGF-I) levels were elevated after 12 or 13 days of microgravity, and a approximately 7% postexercise IGF-I increase was independent of this spaceflight effect. The suppression of the BGH response to exercise during spaceflight indicates that some minimum level of chronic neuromuscular activity and/or loading is necessary to maintain a normal exercise-induced BGH release. Moreover, these results suggest that there is a muscle afferent-pituitary axis that can modulate BGH release.

Effects of spaceflight on rhesus quadrupedal locomotion after return to 1G.

Effects of spaceflight on Rhesus quadrupedal locomotion after return to 1G. Locomotor performance, activation patterns of the soleus (Sol), medial gastrocnemius (MG), vastus lateralis (VL), and tibialis anterior (TA) and MG tendon force during quadrupedal stepping were studied in adult Rhesus before and after 14 days of either spaceflight (n = 2) or flight simulation at 1G (n = 3). Flight simulation involved duplication of the spaceflight conditions and experimental protocol in a 1G environment. Postflight, but not postsimulation, electromyographic (EMG) recordings revealed clonus-like activity in all muscles. Compared with preflight, the cycle period and burst durations of the primary extensors (Sol, MG, and VL) tended to decrease postflight. These decreases were associated with shorter steps. The flexor (TA) EMG burst duration postflight was similar to preflight, whereas the burst amplitude was elevated. Consequently, the Sol:TA and MG:TA EMG amplitude ratios were lower following flight, reflecting a "flexor bias." Together, these alterations in mean EMG amplitudes reflect differential adaptations in motor-unit recruitment patterns of flexors and extensors as well as fast and slow motor pools. Shorter cycle period and burst durations persisted throughout the 20-day postflight testing period, whereas mean EMG returned to preflight levels by 17 days postflight. Compared with presimulation, the simulation group showed slight increases in the cycle period and burst durations of all muscles. Mean EMG amplitude decreased in the Sol, increased in the MG and VL, and was unchanged in the TA. Thus adaptations observed postsimulation were different from those observed postflight, indicating that there was a response unique to the microgravity environment, i.e., the modulations in the nervous system controlling locomotion cannot merely be attributed to restriction of movement but appear to be the result of changes in the interpretation of load-related proprioceptive feedback to the nervous system. Peak MG tendon force amplitudes were approximately two times greater post- compared with preflight or presimulation. Adaptations in tendon force and EMG amplitude ratios indicate that the nervous system undergoes a reorganization of the recruitment patterns biased toward an increased recruitment of fast versus slow motor units and flexor versus extensor muscles. Combined, these data indicate that some details of the control of motor pools during locomotion are dependent on the persistence of Earth's gravitational environment.

Acute and chronic hormonal responses to resistance training designed to promote muscle hypertrophy.

Acute and chronic hormonal responses to resistance training were evaluated in 11 college men who completed 12 weeks (33 sessions) of high volume resistance training. No differences in resting concentrations of growth hormone (GH), insulin-like growth factor-I, testosterone, or sex hormone-binding globulin occurred from pre- and posttraining in the trained vs. nontrained control group. However, cortisol (c) decreased 17% for both groups (p < 0.05). There were no differences in exercise-induced responses between Sessions 10 and 20, with all hormone concentrations increasing (p < 0.05) from pre- at mid- and post exercise session. However, after correction for plasma volume decreases, only C and GH showed differences, with C increased from mid- to postsession (48% 10th; 49% 20th), and GH increased from pre- at mid- and postsession for both sessions 10 (0.16 +/- 0.42 pre; 4.77 +/- 6.24 mid; 6.26 +/- 5.19 post; microg x L-1) and 20 (0.33 +/- 0.85 pre; 5.42 +/- 9.08 mid; 8.24 +/- 7.61 post; microg x L-1). Significant correlations (p< 0.05) existed only between absolute mean GH increases from presession and the degree of muscle fiber hypertrophy for type I (r = 0.70 mid, 0.74 post) and type II (r = 0.71 post) fibers. In conclusion, resistance training had no effect on resting serum hormone concentrations, whereas similar acute exercise responses occurred between the 10th and 20th training sessions.

Sample size required for the accurate determination of fiber area and capillarity of human skeletal muscle.

This study aimed to determine the skeletal muscle fiber sample size required for a reliable, valid representation of an individual's average fiber area and capillary contacts (CC) per fiber. Biopsies were obtained from the biceps brachii of 11 college-age, recreational resistance-trained men in conjunction with a study investigating how muscle morphology changed after 12 weeks of resistance training. The effect of additional measurements on the rolling cumulative means for fiber area and CC per fiber was evaluated using sequential estimation analysis. Results showed that group cumulative mean and standard deviation had stabilized by 50 fiber measurements per individual for type I and II fibers and CC per fiber. Significant correlations (.96-.99; p < .05) existed between the 50th and 95th/100th cumulative individual means. These results indicate that a typical skeletal muscle needle biopsy would be sufficient to characterize type I and II fiber areas and CC per fiber of an individual in most subject populations, although the required sample size for characterizing fiber subtypes might be different.

Maintenance of myonuclear domain size in rat soleus after overload and growth hormone/IGF-I treatment.

The purpose of this study was to determine the effects of functional overload (FO) combined with growth hormone/insulin-like growth factor I (GH/IGF-I) administration on myonuclear number and domain size in rat soleus muscle fibers. Adult female rats underwent bilateral ablation of the plantaris and gastrocnemius muscles and, after 7 days of recovery, were injected three times daily for 14 days with GH/IGF-I (1 mg/kg each; FO + GH/IGF-I group) or saline vehicle (FO group). Intact rats receiving saline vehicle served as controls (Con group). Muscle wet weight was 32% greater in the FO than in the Con group: 162 +/- 8 vs. 123 +/- 16 mg. Muscle weight in the FO + GH/IGF-I group (196 +/- 14 mg) was 59 and 21% larger than in the Con and FO groups, respectively. Mean soleus fiber cross-sectional area of the FO + GH/IGF-I group (2,826 +/- 445 microm2) was increased compared with the Con (2,044 +/- 108 microm2) and FO (2,267 +/- 301 microm2) groups. The difference in fiber size between the FO and Con groups was not significant. Mean myonuclear number increased in FO (187 +/- 15 myonuclei/mm) and FO + GH/IGF-I (217 +/- 23 myonuclei/mm) rats compared with Con (155 +/- 12 myonuclei/mm) rats, although the difference between FO and FO + GH/IGF-I animals was not significant. The mean cytoplasmic volume per myonucleus (myonuclear domain) was similar across groups. These results demonstrate that the larger mean muscle weight and fiber cross-sectional area occurred when FO was combined with GH/IGF-I administration and that myonuclear number increased concomitantly with fiber volume. Thus there appears to be some mechanism(s) that maintains the myonuclear domain when a fiber hypertrophies.

Bed rest suppresses bioassayable growth hormone release in response to muscle activity.

Hormonal responses to muscle activity were studied in eight men before (-13 or -12 and -8 or -7 days), during (2 or 3, 8 or 9, and 13 or 14 days) and after (+2 or +3 and +10 or +11 days) 17 days of bed rest. Muscle activity consisted of a series of unilateral isometric plantar flexions, including 4 maximal voluntary contractions (MVCs), 48 contractions at 30% MVC, and 12 contractions at 80% MVC, all performed at a 4:1-s work-to-rest ratio. Blood was collected before and immediately after muscle activity to measure plasma growth hormone by radioimmunoassay (IGH) and by bioassay (BGH) of tibia epiphyseal cartilage growth in hypophysectomized rats. Plasma IGH was unchanged by muscle activity before, during, or after bed rest. Before bed rest, muscle activity increased (P < 0.05) BGH by 66% at -13 or -12 days (2,146 +/- 192 to 3,565 +/- 197 microg/l) and by 92% at -8 or -7 days (2,162 +/- 159 to 4,161 +/- 204 microg/l). After 2 or 3 days of bed rest, there was no response of BGH to the muscle activity, a pattern that persisted through 8 or 9 days of bed rest. However, after 13 or 14 days of bed rest, plasma concentration of BGH was significantly lower after than before muscle activity (2,594 +/- 211 to 2,085 +/- 109 microg/l). After completion of bed rest, muscle activity increased BGH by 31% at 2 or 3 days (1,807 +/- 117 to 2,379 +/- 473 microg/l; P < 0.05), and by 10 or 11 days the BGH response was similar to that before bed rest (1,881 +/- 75 to 4,160 +/- 315 microg/l; P < 0.05). These data demonstrate that the ambulatory state of an individual can have a major impact on the release of BGH, but not IGH, in response to a single bout of muscle activity.

Muscle fiber hypertrophy, hyperplasia, and capillary density in college men after resistance training.

Twelve male subjects with recreational resistance training backgrounds completed 12 wk of intensified resistance training (3 sessions/wk; 8 exercises/session; 3 sets/exercise; 10 repetitions maximum/set). All major muscle groups were trained, with four exercises emphasizing the forearm flexors. After training, strength (1-repetition maximum preacher curl) increased by 25% (P < 0.05). Magnetic resonance imaging scans revealed an increase in the biceps brachii muscle cross-sectional area (CSA) (from 11.8 +/- 2.7 to 13.3 +/- 2.6 cm2; n = 8; P < 0.05). Muscle biopsies of the biceps brachii revealed increases (P < 0.05) in fiber areas for type I (from 4,196 +/- 859 to 4,617 +/- 1,116 microns2; n = 11) and II fibers (from 6,378 +/- 1,552 to 7,474 +/- 2,017 microns2; n = 11). Fiber number estimated from the above measurements did not change after training (293.2 +/- 61.5 x 10(3) pretraining; 297.5 +/- 69.5 x 10(3) posttraining; n = 8). However, the magnitude of muscle fiber hypertrophy may influence this response because those subjects with less relative muscle fiber hypertrophy, but similar increases in muscle CSA, showed evidence of an increase in fiber number. Capillaries per fiber increased significantly (P < 0.05) for both type I (from 4.9 +/- 0.6 to 5.5 +/- 0.7; n = 10) and II fibers (from 5.1 +/- 0.8 to 6.2 +/- 0.7; n = 10). No changes occurred in capillaries per fiber area or muscle area. In conclusion, resistance training resulted in hypertrophy of the total muscle CSA and fiber areas with no change in estimated fiber number, whereas capillary changes were proportional to muscle fiber growth.