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  • American Physiological Society  (8)
  • 1
    Online Resource
    Online Resource
    Development of models to predict anabolic response to testosterone administration in healthy young men
    American Physiological Society ; 2003
    In:  American Journal of Physiology-Endocrinology and Metabolism Vol. 284, No. 5 ( 2003-05-01), p. E1009-E1017
    Details
    In: American Journal of Physiology-Endocrinology and Metabolism, American Physiological Society, Vol. 284, No. 5 ( 2003-05-01), p. E1009-E1017
    Abstract: Considerable heterogeneity exists in the anabolic response to androgen administration; however, the factors that contribute to variation in an individual's anabolic response to androgens remain unknown. We investigated whether testosterone dose and/or any combination of baseline variables, including concentrations of hormones, age, body composition, muscle function, and morphometry or polymorphisms in androgen receptor could explain the variability in anabolic response to testosterone. Fifty-four young men were treated with a long-acting gonadotropin-releasing hormone (GnRH) agonist and one of five doses (25, 50, 125, 300, or 600 mg/wk) of testosterone enanthate (TE) for 20 wk. Anabolic response was defined as a change in whole body fat-free mass (FFM) by dual-energy X-ray absorptiometry (DEXA), appendicular FFM (by DEXA), and thigh muscle volume (by magnetic resonance imaging) during TE treatment. We used univariate and multivariate analysis to identify the subset of baseline measures that best explained the variability in anabolic response to testosterone supplementation. The three-variable model of TE dose, age, and baseline prostate-specific antigen (PSA) level explained 67% of the variance in change in whole body FFM. Change in appendicular FFM was best explained (64% of the variance) by the linear combination of TE dose, baseline PSA, and leg press strength, whereas TE dose, log of the ratio of luteinizing hormone to testosterone concentration, and age explained 66% of the variation in change in thigh muscle volume. The models were further validated by using Ridge analysis and cross-validation in data subsets. Only the model using testosterone dose, age, and PSA was a consistent predictor of change in FFM in subset analyses. The length of CAG tract was only a weak predictor of change in thigh muscle volume and lean body mass. Hence, the anabolic response of healthy, young men to exogenous testosterone administration can largely be predicted by the testosterone dose.
    Type of Medium: Online Resource
    ISSN: 0193-1849 , 1522-1555
    URL: Article
    DOI: 10.1152/ajpendo.00536.2002
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2003
    detail.hit.zdb_id: 1477331-4
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  • 2
    Online Resource
    Online Resource
    Effects of a supraphysiological dose of testosterone on physical function, muscle performance, mood, and fatigue in men with HIV-associated weight loss
    American Physiological Society ; 2008
    In:  American Journal of Physiology-Endocrinology and Metabolism Vol. 294, No. 6 ( 2008-06), p. E1135-E1143
    Details
    In: American Journal of Physiology-Endocrinology and Metabolism, American Physiological Society, Vol. 294, No. 6 ( 2008-06), p. E1135-E1143
    Abstract: Testosterone increases fat-free mass (FFM) in men infected with human immunodeficiency virus (HIV), but its effects on muscle performance, physical function, mood, and quality of life are poorly understood. Sixty-one HIV-infected men with weight loss were randomized to receive weekly intramuscular injections of 300 mg of testosterone enanthate or placebo for 16 wk. The primary outcome of interest was physical function (walking speed, stair-climbing power, and load-carrying ability). Secondary outcome measures included body weight and composition, muscle performance, sexual function, mood, and quality of life. Serum nadir free and total testosterone levels increased (+188.0 ± 29.6 and +720 ± 86 ng/dl) in the testosterone, but not placebo, group. Testosterone administration was associated with increased FFM (2.8 ± 0.5 kg), which was significantly greater than in the placebo group ( P 〈 0.0001). Leg press strength increased significantly in testosterone-treated ( P = 0.027), but not placebo-treated, men; the difference between groups was not significant. Other measures of muscle performance and physical function did not change significantly in either group. Men receiving testosterone demonstrated significantly greater improvements in mental health and quality-of-life scores than those receiving placebo and improvements in fatigue/energy and mood scores that were not significantly different from those receiving placebo. Sexual function scores did not change in either group. In HIV-infected men with weight loss, a supraphysiological dose of testosterone significantly increased FFM but did not improve self-reported or performance-based measures of physical function. Improvements in mood, fatigue, and quality-of-life measures in the testosterone group, although clinically important, need further confirmation.
    Type of Medium: Online Resource
    ISSN: 0193-1849 , 1522-1555
    URL: Article
    DOI: 10.1152/ajpendo.90213.2008
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2008
    detail.hit.zdb_id: 1477331-4
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  • 3
    Online Resource
    Online Resource
    Skeletal muscle adaptations to testosterone and resistance training in men with COPD
    American Physiological Society ; 2007
    In:  Journal of Applied Physiology Vol. 103, No. 4 ( 2007-10), p. 1299-1310
    Details
    In: Journal of Applied Physiology, American Physiological Society, Vol. 103, No. 4 ( 2007-10), p. 1299-1310
    Abstract: We recently reported increased leg lean mass and strength in men with chronic obstructive pulmonary disease (COPD) receiving 10 wk of testosterone (T) and leg resistance training (R) (Casaburi R, Bhasin S, Cosentino L, Porszasz J, Somfay A, Lewis M, Fournier M, Storer T. Am J Respir Crit Care Med 170: 870–878, 2004). The present study evaluates the role of muscle IGF and related factors as potential mechanisms for our findings, using quadriceps muscle biopsies from the same cohort. Patient groups were 1) weekly placebo (P) injections + no R; 2) P and R; 3) weekly injections of T + no R; and 4) T + R (TR). Muscle fibers were classified histochemically, and their cross-sectional areas (CSAs) and fiber density (number of fibers per unit area) were determined. Gene transcripts were determined by real-time PCR and protein expression by RIA. While no significant changes in fiber CSAs were noted across groups, increased trends were observed after 10 wk, and significant decrements in muscle fiber density were noted in all treated groups. A global increase in all myosin heavy chain (MyHC) mRNA isoforms was observed in TR patients. Muscle IGF-IEa and IGF-IEc mRNAs were significantly increased with TR group. Muscle IGF-I protein was increased in all intervention groups (greatest in TR). While TR IGF-II mRNA was increased, protein levels were unaltered. IGF binding protein-4 mRNA was increased with TR. Myogenin mRNA was increased in both T groups, while MyoD and myostatin were unchanged. Muscle atrophy F-box mRNA tended to increase with TR. Our data suggest that the combined interventions produced an enhanced local anabolic milieu driven in large part by the muscle IGF system, despite potentially negative biochemical influences present in COPD patients.
    Type of Medium: Online Resource
    ISSN: 8750-7587 , 1522-1601
    URL: Article
    DOI: 10.1152/japplphysiol.00150.2007
    RVK:
    WA 15000
    RVK:
    XA 52094
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2007
    detail.hit.zdb_id: 1404365-8
    SSG: 12
    SSG: 31
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  • 4
    Online Resource
    Online Resource
    Testosterone dose-response relationships in healthy young men
    American Physiological Society ; 2001
    In:  American Journal of Physiology-Endocrinology and Metabolism Vol. 281, No. 6 ( 2001-12-01), p. E1172-E1181
    Details
    In: American Journal of Physiology-Endocrinology and Metabolism, American Physiological Society, Vol. 281, No. 6 ( 2001-12-01), p. E1172-E1181
    Abstract: Testosterone increases muscle mass and strength and regulates other physiological processes, but we do not know whether testosterone effects are dose dependent and whether dose requirements for maintaining various androgen-dependent processes are similar. To determine the effects of graded doses of testosterone on body composition, muscle size, strength, power, sexual and cognitive functions, prostate-specific antigen (PSA), plasma lipids, hemoglobin, and insulin-like growth factor I (IGF-I) levels, 61 eugonadal men, 18–35 yr, were randomized to one of five groups to receive 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 of testosterone enanthate for 20 wk. Energy and protein intakes were standardized. The administration of the GnRH agonist plus graded doses of testosterone resulted in mean nadir testosterone concentrations of 253, 306, 542, 1,345, and 2,370 ng/dl at the 25-, 50-, 125-, 300-, and 600-mg doses, respectively. Fat-free mass increased dose dependently in men receiving 125, 300, or 600 mg of testosterone weekly (change +3.4, 5.2, and 7.9 kg, respectively). The changes in fat-free mass were highly dependent on testosterone dose ( P = 0.0001) and correlated with log testosterone concentrations ( r = 0.73, P = 0.0001). Changes in leg press strength, leg power, thigh and quadriceps muscle volumes, hemoglobin, and IGF-I were positively correlated with testosterone concentrations, whereas changes in fat mass and plasma high-density lipoprotein (HDL) cholesterol were negatively correlated. Sexual function, visual-spatial cognition and mood, and PSA levels did not change significantly at any dose. We conclude that changes in circulating testosterone concentrations, induced by GnRH agonist and testosterone administration, are associated with testosterone dose- and concentration-dependent changes in fat-free mass, muscle size, strength and power, fat mass, hemoglobin, HDL cholesterol, and IGF-I levels, in conformity with a single linear dose-response relationship. However, different androgen-dependent processes have different testosterone dose-response relationships.
    Type of Medium: Online Resource
    ISSN: 0193-1849 , 1522-1555
    URL: Article
    DOI: 10.1152/ajpendo.2001.281.6.E1172
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2001
    detail.hit.zdb_id: 1477331-4
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  • 5
    Online Resource
    Online Resource
    Testosterone-induced increase in muscle size in healthy young men is associated with muscle fiber hypertrophy
    American Physiological Society ; 2002
    In:  American Journal of Physiology-Endocrinology and Metabolism Vol. 283, No. 1 ( 2002-07-01), p. E154-E164
    Details
    In: American Journal of Physiology-Endocrinology and Metabolism, American Physiological Society, Vol. 283, No. 1 ( 2002-07-01), p. E154-E164
    Abstract: 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 μm 2 , P 〈 0.05 at 300-mg dose, and 3,347 ± 253 vs. 4,984 ± 374 μm 2 , 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 μm 2 , 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.
    Type of Medium: Online Resource
    ISSN: 0193-1849 , 1522-1555
    URL: Article
    DOI: 10.1152/ajpendo.00502.2001
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2002
    detail.hit.zdb_id: 1477331-4
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  • 6
    Online Resource
    Online Resource
    Metabolic and morphometric profile of muscle fibers in chronic hemodialysis patients
    American Physiological Society ; 2012
    In:  Journal of Applied Physiology Vol. 112, No. 1 ( 2012-01-01), p. 72-78
    Details
    In: Journal of Applied Physiology, American Physiological Society, Vol. 112, No. 1 ( 2012-01-01), p. 72-78
    Abstract: Muscle weakness and effort intolerance are common in maintenance hemodialysis (MHD) patients. This study characterized morphometric, histochemical, and biochemical properties of limb muscle in MHD patients compared with controls (CTL) with similar age, gender, and ethnicity. Vastus lateralis muscle biopsies were obtained from 60 MHD patients, 1 day after dialysis, and from 21 CTL. Muscle fiber types and capillaries were identified immunohistochemically. Individual muscle fiber cross-sectional areas (CSA) were quantified. Individual fiber oxidative capacities were determined (microdensitometric assay) to measure succinate dehydrogenase (SDH) activity. Mean CSAs of type I, IIA, and IIX fibers were 33, 26, and 28% larger in MHD patients compared with CTL. SDH activities for type I, IIA, and IIX fibers were reduced by 29, 40, and 47%, respectively, in MHD. Capillary to fiber ratio was increased by 11% in MHD. The number of capillaries surrounding individual fiber types were also increased (type I: 9%; IIA: 10%; IIX: 23%) in MHD patients. However, capillary density (capillaries per unit muscle fiber area) was reduced by 34% in MHD patients, compared with CTL. Ultrastuctural analysis revealed swollen mitochondria with dense matrix in MHD patients. These results highlight impaired oxidative capacity and capillarity in MHD patients. This would be expected to impair energy production as well as substrate and oxygen delivery and exchange and contribute to exercise intolerance. The enlarged CSA of muscle fibers may, in part, be accounted for by edema. We speculate that these changes contribute to reduce limb strength in MHD patients by reducing specific force.
    Type of Medium: Online Resource
    ISSN: 8750-7587 , 1522-1601
    URL: Article
    DOI: 10.1152/japplphysiol.00556.2011
    RVK:
    WA 15000
    RVK:
    XA 52094
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2012
    detail.hit.zdb_id: 1404365-8
    SSG: 12
    SSG: 31
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  • 7
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    Effect of endurance and/or strength training on muscle fiber size, oxidative capacity, and capillarity in hemodialysis patients
    American Physiological Society ; 2015
    In:  Journal of Applied Physiology Vol. 119, No. 8 ( 2015-10-15), p. 865-871
    Details
    In: Journal of Applied Physiology, American Physiological Society, Vol. 119, No. 8 ( 2015-10-15), p. 865-871
    Abstract: We previously reported reduced limb muscle fiber succinate dehydrogenase (SDH) activity and capillarity density and increased cross-sectional areas (CSAs) of all fiber types in maintenance hemodialysis (MHD) patients compared with matched controls that may contribute to their effort intolerance and muscle weakness. This study evaluated whether endurance training (ET), strength training (ST), or their combination (EST) alters these metabolic and morphometric aberrations as a mechanism for functional improvement. Five groups were evaluated: 1) controls; 2) MHD/no training; 3) MHD/ET; 4) MHD/ST; and 5) MHD/EST. Training duration was 21.5 ± 0.7 wk. Vastus lateralis muscle biopsies were obtained after HD at baseline and at study end. Muscle fibers were classified immunohistochemically, and fiber CSAs were computed. Individual fiber SDH activity was determined by a microdensitometric assay. Capillaries were identified using antibodies against endothelial cells. Type I and IIA fiber CSAs decreased significantly (10%) with EST. In the ET group, SDH activity increased 16.3% in type IIA and 19.6% in type IIX fibers. Capillary density increased significantly by 28% in the EST group and 14.3% with ET. The number of capillaries surrounding individual fiber type increased significantly in EST and ET groups. Capillary-to-fiber ratio increased significantly by 11 and 9.6% in EST and ET groups, respectively. We conclude that increments in capillarity and possibly SDH activity in part underlie improvements in endurance of MHD patients posttraining. We speculate that improved specific force and/or neural adaptations to exercise underlie improvements in limb muscle strength of MHD patients.
    Type of Medium: Online Resource
    ISSN: 8750-7587 , 1522-1601
    URL: Article
    DOI: 10.1152/japplphysiol.01084.2014
    RVK:
    WA 15000
    RVK:
    XA 52094
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2015
    detail.hit.zdb_id: 1404365-8
    SSG: 12
    SSG: 31
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  • 8
    Online Resource
    Online Resource
    Effects of an oral androgen on muscle and metabolism in older, community-dwelling men
    American Physiological Society ; 2003
    In:  American Journal of Physiology-Endocrinology and Metabolism Vol. 284, No. 1 ( 2003-01-01), p. E120-E128
    Details
    In: American Journal of Physiology-Endocrinology and Metabolism, American Physiological Society, Vol. 284, No. 1 ( 2003-01-01), p. E120-E128
    Abstract: To determine whether oxymetholone increases lean body mass (LBM) and skeletal muscle strength in older persons, 31 men 65–80 yr of age were randomized to placebo ( group 1) or 50 mg ( group 2) or 100 mg ( group 3) daily for 12 wk. For the three groups, total LBM increased by 0.0 ± 0.6, 3.3 ± 1.2 ( P 〈 0.001), and 4.2 ± 2.4 kg ( P 〈 0.001), respectively. Trunk fat decreased by 0.2 ± 0.4, 1.7 ± 1.0 ( P = 0.018), and 2.2 ± 0.9 kg ( P= 0.005) in groups 1, 2, and 3, respectively. Relative increases in 1-repetition maximum (1-RM) strength for biaxial chest press of 8.2 ± 9.2 and 13.9 ± 8.1% in the two active treatment groups were significantly different from the change (−0.8 ± 4.3%) for the placebo group ( P 〈 0.03). For lat pull-down, 1-RM changed by −0.6 ± 8.3, 8.8 ± 15.1, and 18.4 ± 21.0% for the groups, respectively (1-way ANOVA, P = 0.019). The pattern of changes among the groups for LBM and upper-body strength suggested that changes might be related to dose. Alanine aminotransferase increased by 72 ± 67 U/l in group 3 ( P 〈 0.001), and HDL-cholesterol decreased by −19 ± 9 and −23 ± 18 mg/dl in groups 2 and 3, respectively ( P = 0.04 and P = 0.008). Thus oxymetholone improved LBM and maximal voluntary muscle strength and decreased fat mass in older men.
    Type of Medium: Online Resource
    ISSN: 0193-1849 , 1522-1555
    URL: Article
    DOI: 10.1152/ajpendo.00363.2002
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2003
    detail.hit.zdb_id: 1477331-4
    SSG: 12
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