Testosterone-induced increase in muscle size in healthy young men is associated with muscle fiber hypertrophy

2002 ◽  
Vol 283 (1) ◽  
pp. E154-E164 ◽  
Author(s):  
Indrani Sinha-Hikim ◽  
Jorge Artaza ◽  
Linda Woodhouse ◽  
Nestor Gonzalez-Cadavid ◽  
Atam B. Singh ◽  
...  

Administration of replacement doses of testosterone to healthy hypogonadal men and supraphysiological doses to eugonadal men increases muscle size. To determine whether testosterone-induced increase in muscle size is due to muscle fiber hypertrophy, 61 healthy men, 18–35 yr of age, received monthly injections of a long-acting gonadotropin-releasing hormone (GnRH) agonist to suppress endogenous testosterone secretion and weekly injections of 25, 50, 125, 300, or 600 mg testosterone enanthate (TE) for 20 wk. Thigh muscle volume was measured by magnetic resonance imaging (MRI) scan, and muscle biopsies were obtained from vastus lateralis muscle in 39 men before and after 20 wk of combined treatment with GnRH agonist and testosterone. Administration of GnRH agonist plus TE resulted in mean nadir testosterone concentrations of 234, 289, 695, 1,344, and 2,435 ng/dl at the 25-, 50-, 125-, 300-, and 600-mg doses, respectively. Graded doses of testosterone administration were associated with testosterone dose and concentration-dependent increase in muscle volume measured by MRI (changes in vastus lateralis volume, −4, +7, +15, +32, and +48 ml at 25-, 50-, 125-, 300-, and 600-mg doses, respectively). Changes in cross-sectional areas of both type I and II fibers were dependent on testosterone dose and significantly correlated with total ( r = 0.35, and 0.44, P < 0.0001 for type I and II fibers, respectively) and free ( r = 0.34 and 0.35, P < 0.005) testosterone concentrations during treatment. The men receiving 300 and 600 mg of TE weekly experienced significant increases from baseline in areas of type I (baseline vs. 20 wk, 3,176 ± 186 vs. 4,201 ± 252 μm2, P < 0.05 at 300-mg dose, and 3,347 ± 253 vs. 4,984 ± 374 μm2, P = 0.006 at 600-mg dose) muscle fibers; the men in the 600-mg group also had significant increments in cross-sectional area of type II (4,060 ± 401 vs. 5,526 ± 544 μm2, P = 0.03) fibers. The relative proportions of type I and type II fibers did not change significantly after treatment in any group. The myonuclear number per fiber increased significantly in men receiving the 300- and 600-mg doses of TE and was significantly correlated with testosterone concentration and muscle fiber cross-sectional area. In conclusion, the increases in muscle volume in healthy eugonadal men treated with graded doses of testosterone are associated with concentration-dependent increases in cross-sectional areas of both type I and type II muscle fibers and myonuclear number. We conclude that the testosterone induced increase in muscle volume is due to muscle fiber hypertrophy.

Sports ◽  
2019 ◽  
Vol 7 (7) ◽  
pp. 169 ◽  
Author(s):  
Kevin M. Carroll ◽  
Caleb D. Bazyler ◽  
Jake R. Bernards ◽  
Christopher B. Taber ◽  
Charles A. Stuart ◽  
...  

The purpose of the study was to compare the physiological responses of skeletal muscle to a resistance training (RT) program using repetition maximum (RM) or relative intensity (RISR). Fifteen well-trained males underwent RT 3 d·wk−1 for 10 weeks in either an RM group (n = 8) or RISR group (n = 7). The RM group achieved a relative maximum each day, while the RISR group trained based on percentages. The RM group exercised until muscular failure on each exercise, while the RISR group did not reach muscular failure throughout the intervention. Percutaneous needle biopsies of the vastus lateralis were obtained pre-post the training intervention, along with ultrasonography measures. Dependent variables were: Fiber type-specific cross-sectional area (CSA); anatomical CSA (ACSA); muscle thickness (MT); mammalian target of rapamycin (mTOR); adenosine monophosphate protein kinase (AMPK); and myosin heavy chains (MHC) specific for type I (MHC1), type IIA (MHC2A), and type IIX (MHC2X). Mixed-design analysis of variance and effect size using Hedge’s g were used to assess within- and between-group alterations. RISR statistically increased type I CSA (p = 0.018, g = 0.56), type II CSA (p = 0.012, g = 0.81), ACSA (p = 0.002, g = 0.53), and MT (p < 0.001, g = 1.47). RISR also yielded a significant mTOR reduction (p = 0.031, g = −1.40). Conversely, RM statistically increased only MT (p = 0.003, g = 0.80). Between-group effect sizes supported RISR for type I CSA (g = 0.48), type II CSA (g = 0.50), ACSA (g = 1.03), MT (g = 0.72), MHC2X (g = 0.31), MHC2A (g = 0.87), and MHC1 (g = 0.59); with all other effects being of trivial magnitude (g < 0.20). Our results demonstrated greater adaptations in fiber size, whole-muscle size, and several key contractile proteins when using RISR compared to RM loading paradigms.


2022 ◽  
pp. 110956
Author(s):  
Marcel B. Lanza ◽  
Hugo C. Martins-Costa ◽  
Carolina C. De Souza ◽  
Fernando V. Lima ◽  
Rodrigo C. Diniz ◽  
...  

1992 ◽  
Vol 73 (3) ◽  
pp. 812-816 ◽  
Author(s):  
A. Aniansson ◽  
G. Grimby ◽  
M. Hedberg

Muscle strength and muscle morphology have been studied three times during a period of 11 yr in nine elderly men. On the last occasion the average age was 80.4 (range 79–82) yr. Body cell mass decreased by 6% and muscle strength for knee extension, measured by means of isometric and concentric isokinetic (30–60 degrees/s) recordings, declined by 25–35% over the 11-yr period. Between 76 and 80 yr of age only the isokinetic strength for 30 degrees/s decreased significantly. Muscle fiber composition in the vastus lateralis did not change between 69 and 76 yr of age, but there was a significant reduction in the proportion of type IIb fibers from 76 to 80 yr. The decrease in type II fiber areas was not significant between 69 and 76 yr of age (as in a larger sample from the same population), but a significant increase in both type I and type II fiber areas was recorded from 76 to 80 yr of age and biceps brachii showed similar tendencies. In the same period, the enzymatic activities of myokinase and lactate dehydrogenase subsided in the vastus lateralis, but there was no change for triose phosphate dehydrogenase, 3-hydroxy-CoA-dehydrogenase, and citrate synthase. The muscle fiber hypertrophy in this group of elderly men with maintained physical activity between 76 and 80 yr of age is interpreted as a compensatory adaptation for the loss of motor units. In addition, the adaptation with respect to oxidative capacities seems to be maintained at this age.


1994 ◽  
Vol 77 (2) ◽  
pp. 947-955 ◽  
Author(s):  
M. I. Lewis ◽  
S. A. Monn ◽  
W. Z. Zhan ◽  
G. C. Sieck

Interactive effects of emphysema (EMP) and prolonged nutritional deprivation (ND) on contractile, morphometric, and metabolic properties of hamster diaphragm muscle (DIA) were examined. Six months after induction of EMP (intratracheal elastase), saline-treated controls (CTL) and EMP hamsters of similar body weights were subjected to ND over 6 wk. Isometric contractile and fatigue properties of costal DIA were determined in vitro. DIA fibers were histochemically classified as type I or II, and fiber succinate dehydrogenase activity and cross-sectional area were determined using quantitative microscopic procedures. From histochemical sections, the number of capillaries per fiber (C/F) and per fiber cross-sectional area (C/A) were determined. ND resulted in progressive loss of body weight (ND-CTL, 23.8%; ND-EMP, 28.4%; P = NS). ND did not affect reduction in optimal length (Lo) of DIA fibers in EMP compared with CTL and ND-CTL hamsters. Maximum specific force (i.e., force/unit area) was reduced by approximately 25% in EMP animals compared with CTL. ND did not improve or exacerbate the reduction in specific force with EMP. ND attenuated improved fatigue resistance of DIA in EMP animals. No differences in fiber type proportions were noted among experimental groups. Significant atrophy of type I and II DIA fibers was noted after ND. Atrophy was proportionately greater in type II fibers of ND-EMP when referenced to EMP animals. Thus adaptive hypertrophy of type II DIA fibers in EMP animals was abolished. Fiber succinate dehydrogenase activity was significantly increased in type I and II fibers in EMP DIA. ND did not affect this metabolic adaptation of DIA fibers to persistent loads imposed by EMP.(ABSTRACT TRUNCATED AT 250 WORDS)


1984 ◽  
Vol 57 (5) ◽  
pp. 1399-1403 ◽  
Author(s):  
J. D. MacDougall ◽  
D. G. Sale ◽  
S. E. Alway ◽  
J. R. Sutton

Muscle fiber numbers were estimated in vivo in biceps brachii in 5 elite male bodybuilders, 7 intermediate caliber bodybuilders, and 13 age-matched controls. Mean fiber area and collagen volume density were calculated from needle biopsies and muscle cross-sectional area by computerized tomographic scanning. Contralateral measurements in a subsample of seven subjects indicated the method for estimation of fiber numbers to have adequate reliability. There was a wide interindividual range for fiber numbers in biceps (172,085–418,884), but despite large differences in muscle size both bodybuilder groups possessed the same number of muscle fibers as the group of untrained controls. Although there was a high correlation between average cross-sectional fiber area and total muscle cross-sectional area within each group, many of the subjects with the largest muscles also tended to have a large number of fibers. Since there were equally well-trained subjects with fewer than normal fiber numbers, we interpret this finding to be due to genetic endowment rather than to training-induced hyperplasia. The proportion of muscle comprised of connective and other noncontractile tissue was the same for all subjects (approximately 13%), thus indicating greater absolute amounts of connective tissue in the trained subjects. We conclude that in humans, heavy resistance training directed toward achieving maximum size in skeletal muscle does not result in an increase in fiber numbers.


1993 ◽  
Vol 74 (2) ◽  
pp. 742-749 ◽  
Author(s):  
D. J. Prezant ◽  
D. E. Valentine ◽  
H. H. Kim ◽  
E. I. Gentry

The effects of 4.5 days of acute starvation, either alone or followed by refeeding (ad libitum), on diaphragm contractility, fatigue, and fiber types were studied in male rats. Contractility and fatigue resistance indexes were measured in an in vitro costal diaphragm strip preparation with direct stimulation at 37 degrees C. Compared with controls, starvation produced a 28 +/- 1% (P < 0.001) reduction in body weight and an 18 +/- 4% (P < 0.001) reduction in costal diaphragm weight. Twitch and tetanic tensions (normalized for weight or cross-sectional area) were not reduced by starvation. Starvation produced significant increases in fatigue resistance indexes after a 5-Hz stimulation paradigm but not after a 100-Hz paradigm, supporting the hypothesis that fatigue resistance is dependent on the energy demand of a given paradigm. The proportions of type I and type II fibers were similar between diaphragms of starved and control rats, but the cross-sectional area of type II fibers decreased significantly by 18 +/- 7% (P < 0.01). Thus, despite the significant decrease in diaphragm weight after starvation, contractility was preserved and fatigue resistance was increased (low-output paradigm). This is consistent with the decrease in type II fiber area. Refeeding restored all parameters so that there were no longer significant differences in body or diaphragm weight, contractility, fatigue, or fiber types.


2004 ◽  
Vol 5 (3) ◽  
pp. 195-202 ◽  
Author(s):  
Alissa Guildner Gehrke ◽  
Margaret Sheie Krull ◽  
Robin Shotwell McDonald ◽  
Tracy Sparby ◽  
Jessica Thoele ◽  
...  

Age-related changes in skeletal muscle, in combination with bed rest, may result in a poorer rehabilitation potential for an elderly patient. The purpose of this study was to determine the effects of non-weight bearing (hind limb unweighting [HU]) on the soleus and extensor digitorum longus (EDL) in older rats. Two non-weight bearing conditions were used: an uninterrupted bout of HU and an interrupted bout of HU. Twenty-one rats were randomly placed into 1 of 3 groups: control, interrupted HU (2 phases of 7 days of HU, separated by a 4-day weight-bearing phase) and an uninterrupted HU (18 uninterrupted days of HU). Following non-weight bearing, the soleus and EDL muscles were removed. Fiber type identification was performed by myofibrillar ATPase and cross-sectional area was determined. The findings suggest that any period of non-weight bearing leads to a decrease in muscle wet weight (19%-45%). Both type I and type II fibers of the soleus showed atrophy (decrease in cross-sectional area, 35%-44%) with an uninterrupted bout of non-weight bearing. Only the type II fibers of the soleus showed recovery with an interrupted bout of weight bearing. In the EDL, type II fibers were more affected by an uninterrupted bout of non-weight bearing (15% decrease in fiber size) compared to the type I fibers. EDL type II fibers showed more atrophy with interrupted bouts of non-weight bearing than with a single bout (a 40% compared to a 15% decrease). This study shows that initial weight bearing after an episode of non-weight bearing may be damaging to type II fibers of the EDL.


2022 ◽  
Vol 12 ◽  
Author(s):  
Garrett M. Hester ◽  
Trisha A. VanDusseldorp ◽  
Phuong L. Ha ◽  
Kaveh Kiani ◽  
Alex A. Olmos ◽  
...  

Introduction: The increasingly popular microbiopsy is an appealing alternative to the more invasive Bergström biopsy given the challenges associated with harvesting skeletal muscle in older populations. Parameters of muscle fiber morphology and composition derived from the microbiopsy have not been compared between young and older adults.Purpose: The purpose of this study was to examine muscle fiber morphology and composition in young (YM) and older (OM) males using the microbiopsy sampling technique. A secondary aim was to determine if specific strength is associated with serum levels of C-terminal agrin fragment [CAF; an indicator of neuromuscular junction (NMJ) degradation].Methods: Thirty healthy, YM (n = 15, age = 20.7 ± 2.2 years) and OM (n = 15, age = 71.6 ± 3.9 years) underwent ultrasound imaging to determine whole-muscle cross-sectional area (CSA) of the vastus lateralis and rectus femoris as well as isometric and isokinetic (60°⋅s–1 and 180°⋅s–1) peak torque testing of the knee extensors. Microbiopsy samples of the vastus lateralis were collected from 13 YM and 11 OM, and immunofluorescence was used to calculate CSA and proportion of type I and type II fibers.Results: Peak torque was lower in OM at all velocities (p ≤ 0.001; d = 1.39–1.86) but only lower at 180°⋅s–1 (p = 0.003; d = 1.23) when normalized to whole-muscle CSA. Whole-muscle CSA was smaller in OM (p = 0.001; d = 1.34), but atrophy was not present at the single fiber level (p &gt; 0.05). Per individual, ∼900 fibers were analyzed, and type I fiber CSA was larger (p = 0.05; d = 0.94) in OM which resulted in a smaller type II/I fiber CSA ratio (p = 0.015; d = 0.95). CAF levels were not sensitive to age (p = 0.159; d = 0.53) nor associated with specific strength or whole-muscle CSA in OM.Conclusion: The microbiopsy appears to be a viable alternative to the Bergström biopsy for histological analyses of skeletal muscle in older adults. NMJ integrity was not influential for age-related differences in specific strength in our healthy, non-sarcopenic older sample.


2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 354-354
Author(s):  
Maslyn A Greene ◽  
Aliute Udoka ◽  
Rhonda Powell ◽  
Rooksana Noorai ◽  
Terri Bruce ◽  
...  

Abstract The objective of this study was to evaluate the miRNA transcriptome and muscle fiber characteristics of lambs from ewes consuming endophyte-infected tall fescue (E+) seed during two stages of gestation at two animal ages. Pregnant Suffolk ewes (yr 1 n = 36; yr 2 n = 60) were randomly assigned to one of two gestational treatments: E+ seed (1.77 mg/hd/d of ergovaline/ergovalinine) during mid- (gd 35 - 85; MID) or late-gestation (gd 86 – 133/parturition; LATE). Longissimus muscle samples (n = 3/E+ treatment/time) were collected from fetuses on gd 133 (FETAL; expt. 1) or from wethers after finishing to market weight (MKT; expt. 2) from ewes from MID and LATE E+ treatments. Data were analyzed as a 2 x 2 factorial with E+ treatment (MID or LATE), time (FETAL or MKT), and the two-way interaction in the model. Exposure to E+ fescue seed during LATE gestation reduced (P = 0.03) cross-sectional area of Type II muscle fibers at MKT but not at FETAL. Cross-sectional area of Type II muscle fibers were larger (P &lt; 0.05) at MKT than FETAL. Animal age influenced miRNA expression with 120 miRNA differentially expressed. miRNA-22-3p and -29a were down regulated (P &lt; 0.001; &gt; -5 log fold change) with animal age; whereas miR-3958-3p, -410-3p, -299-5p and -487b-3p (P &lt; 0.0001; &gt; 3 log fold change) were up-regulated. Exposure to E+ during MID or LATE gestation did not alter miRNA expression. Muscle fiber hypertrophy increased from FETAL to MKT age altered the expression of miRNA in longissimus muscle.


1996 ◽  
Vol 81 (1) ◽  
pp. 145-151 ◽  
Author(s):  
D. L. Allen ◽  
W. Yasui ◽  
T. Tanaka ◽  
Y. Ohira ◽  
S. Nagaoka ◽  
...  

The effects of 14 days of spaceflight on myonuclear number, fiber size, and myosin heavy chain (MHC) expression in isolated rat soleus muscle fiber segments were studied. Single soleus muscle fibers from rats flown on the Spacelab Life Sciences-2 14-day mission were compared with those from age-matched ground-based control rats by using confocal microscopy and gel electrophoresis. Spaceflight resulted in a significant reduction in the number of fibers expressing type I MHC and an increase in the number of fibers expressing type IIx or IIa MHC. Space-flight also resulted in an increase in the percentage of fibers coexpressing more than one MHC and in the reexpression of the neonatal isoform of MHC in some fibers. Fiber cross-sectional area was significantly reduced in pure type I MHC-expressing fibers and in fibers coexpressing type I+II MHC but not in fibers expressing one or more type II MHC in the flight rats. The number of myonuclei per millimeter was significantly reduced in type I MHC-expressing fibers from the flight rats but was not significantly different in type I+II and type II MHC-coexpressing fibers. Fibers expressing neonatal MHC were similar in size to control fibers but had significantly fewer myonuclei per millimeter than flight fibers not expressing neonatal MHC. In type I MHC-expressing fibers, the reduction in fiber cross-sectional area was greater than the reduction in myonuclear number; thus the average cytoplasmic volume per myonucleus was significantly lower in flight than in control fibers. The reduction in both myonuclear number and fiber size of fibers expressing type I MHC after 14 days of spaceflight supports the hypothesis that changes in the number of myonuclei may be a contributing factor to the reduction in fiber size associated with chronic unloading of the musculature.


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