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Efficacy of Testosterone plus NASA Exercise Countermeasures during Head-Down Bed Rest.

ABSTRACT: INTRODUCTION:Prolonged confinement to head-down bed rest (HDBR) results in musculoskeletal losses similar to those observed during long-duration space flight. Exercise countermeasures by themselves have not completely prevented the deleterious losses in muscle mass or function in HDBR or space flight. PURPOSE:The objective was to investigate the safety and efficacy of intermittent, low-dose testosterone treatment in conjunction with NASA exercise (SPRINT) countermeasures during 70 d of 6° HDBR. METHODS:Healthy men (35 ± 8 yr) were randomized into one of three groups that remained inactive (CON) or performed exercise 6 d·wk in addition to receiving either placebo (PEX) or testosterone treatment (TEX, 100 mg·wk). Testosterone/placebo injections were administered once a week for 2 wk, followed by 2 wk off and so on, during HDBR. RESULTS:Total, leg, and trunk lean body mass (LBM) consistently decreased in CON, increased in TEX, and had little or no changes in PEX. Total, leg, and trunk fat mass consistently increased in CON and PEX and decreased in TEX. Leg strength decreased in CON, whereas PEX and TEX were protected against loss in strength. Changes in leg LBM correlated positively with changes in leg muscle strength. CONCLUSIONS:Addition of a testosterone countermeasure enhanced the preventative actions of exercise against body composition changes during long-term HDBR in healthy eugonadal men. This is the first report to demonstrate that cycled, low-dose testosterone treatment increases LBM under conditions of strict exercise control. These results are clinically relevant to the development of safe and effective therapies against muscle atrophy during long-term bed rest, aging, and disease where loss of muscle mass and strength is a risk. The potential space flight applications of such countermeasure combinations deserve further investigations.

SUBMITTER: Dillon EL

PROVIDER: S-EPMC6095739 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Efficacy of Testosterone plus NASA Exercise Countermeasures during Head-Down Bed Rest.

Dillon E Lichar EL Sheffield-Moore Melinda M Durham William J WJ Ploutz-Snyder Lori L LL Ryder Jeffrey W JW Danesi Christopher P CP Randolph Kathleen M KM Gilkison Charles R CR Urban Randall J RJ

Medicine and science in sports and exercise 20180901 9

<h4>Introduction</h4>Prolonged confinement to head-down bed rest (HDBR) results in musculoskeletal losses similar to those observed during long-duration space flight. Exercise countermeasures by themselves have not completely prevented the deleterious losses in muscle mass or function in HDBR or space flight.<h4>Purpose</h4>The objective was to investigate the safety and efficacy of intermittent, low-dose testosterone treatment in conjunction with NASA exercise (SPRINT) countermeasures during 70 ...[more]

PMID: 29924745

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Project description:Microgravity has a dramatic impact on human physiology, illustrated in particular with skeletal muscle impairment. A thorough understanding of the mechanisms leading to loss of muscle mass and structural disorders is necessary for the definition of efficient clinical and spaceflight countermeasures. We investigated the effects of long-term bed rest on transcriptome of soleus (SOL) and vastus lateralis (VL) muscles in healthy women (BRC group, n=8), and the potential beneficial impact of protein supplementation (BRN group, n=8) and of a combined resistance and aerobic training (BRE group, n=8). Gene expression profiles were obtained using an in-house made microarray containing 6681 muscles-relevant genes. A two-class statistical analysis was applied on the 2103 genes with consolidated expression. We identified 472 and 207 modified genes, respectively for SOL and VL in BRC group. Further clustering approaches, identifying relevant biological mechanisms or pathways, underlined five main subclusters. Three are composed almost of upregulated genes involved mainly in nucleic acid and protein metabolism, and two composed almost of downregulated genes involved in energy metabolism. Exercise countermeasure demonstrated a drastic compensatory effect, decreasing the number of differentially-expressed genes by 89 and 96% in SOL and VL. In contrast, nutrition countermeasure had a moderate effect and decreased the number of differentially-expressed genes by 40 and 25% in SOL and VL. Our results allowed reporting a systematic, global and comprehensive view of long-term woman muscle atrophy and brought new lights and insights for space environment and for women who undergo a long-term clinical bed rest. Biological samples were collected from Pre- and Post- bed rest (BR) soleus and vastus lateralis biopsies of each subject from the three groups (bed rest only: BRC; Exercise: BRE; Nutrition: BRN). six technical replicate values (2 duplicate hybridizations âa et bâ to chips with triplicate spots âxxxâ) were obtained for each skeletal muscle sample. Thus for each subject, 12 expression measurements (6 before BR and 6 after BR) were obtained for each muscle.

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Efficacy of Testosterone plus NASA Exercise Countermeasures during Head-Down Bed Rest.

Publications

Efficacy of Testosterone plus NASA Exercise Countermeasures during Head-Down Bed Rest.

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