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  • Gharahdaghi, NimaMRC-Verus Arthritis Centre for Musculoskeletal Ageing Research and Nottingham NIHR BRC, School of Medicine, University of Nottingham, Derby, UK (author)

Pharmacological hypogonadism impairs molecular transducers of exercise-induced muscle growth in humans

  • Article/chapterEnglish2022

Publisher, publication year, extent ...

  • 2022-03
  • John Wiley & Sons,2022
  • printrdacarrier

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  • LIBRIS-ID:oai:DiVA.org:oru-97743
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-97743URI
  • https://doi.org/10.1002/jcsm.12843DOI

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  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Funding agency:Medical Research Council as part of the MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research MR/R502364/1 MR/P021220/1
  • BACKGROUND: The relative role of skeletal muscle mechano-transduction in comparison with systemic hormones, such as testosterone (T), in regulating hypertrophic responses to exercise is contentious. We investigated the mechanistic effects of chemical endogenous T depletion adjuvant to 6 weeks of resistance exercise training (RET) on muscle mass, function, myogenic regulatory factors, and muscle anabolic signalling in younger men.METHODS: Non-hypogonadal men (n = 16; 18-30 years) were randomized in a double-blinded fashion to receive placebo (P, saline n = 8) or the GnRH analogue, Goserelin [Zoladex (Z), 3.6 mg, n = 8], injections, before 6 weeks of supervised whole-body RET. Participants underwent dual-energy X-ray absorptiometry (DXA), ultrasound of m. vastus lateralis (VL), and VL biopsies for assessment of cumulative muscle protein synthesis (MPS), myogenic gene expression, and anabolic signalling pathway responses.RESULTS: Zoladex suppressed endogenous T to within the hypogonadal range and was well tolerated; suppression was associated with blunted fat free mass [Z: 55.4 ± 2.8 to 55.8 ± 3.1 kg, P = 0.61 vs. P: 55.9 ± 1.7 to 57.4 ± 1.7 kg, P = 0.006, effect size (ES) = 0.31], composite strength (Z: 40 ± 2.3% vs. P: 49.8 ± 3.3%, P = 0.03, ES = 1.4), and muscle thickness (Z: 2.7 ± 0.4 to 2.69 ± 0.36 cm, P > 0.99 vs. P: 2.74 ± 0.32 to 2.91 ± 0.32 cm, P < 0.0001, ES = 0.48) gains. Hypogonadism attenuated molecular transducers of muscle growth related to T metabolism (e.g. androgen receptor: Z: 1.2 fold, P > 0.99 vs. P: 1.9 fold, P < 0.0001, ES = 0.85), anabolism/myogenesis (e.g. IGF-1Ea: Z: 1.9 fold, P = 0.5 vs. P: 3.3 fold, P = 0.0005, ES = 0.72; IGF-1Ec: Z: 2 fold, P > 0.99 vs. P: 4.7 fold, P = 0.0005, ES = 0.68; myogenin: Z: 1.3 fold, P > 0.99 vs. P: 2.7 fold, P = 0.002, ES = 0.72), RNA/DNA (Z: 0.47 ± 0.03 to 0.53 ± 0.03, P = 0.31 vs. P: 0.50 ± 0.01 to 0.64 ± 0.04, P = 0.003, ES = 0.72), and RNA/ASP (Z: 5.8 ± 0.4 to 6.8 ± 0.5, P > 0.99 vs. P: 6.5 ± 0.2 to 8.9 ± 1.1, P = 0.008, ES = 0.63) ratios, as well as acute RET-induced phosphorylation of growth signalling proteins (e.g. AKTser473 : Z: 2.74 ± 0.6, P = 0.2 vs. P: 5.5 ± 1.1 fold change, P < 0.001, ES = 0.54 and mTORC1ser2448 : Z: 1.9 ± 0.8, P > 0.99 vs. P: 3.6 ± 1 fold change, P = 0.002, ES = 0.53). Both MPS (Z: 1.45 ± 0.11 to 1.50 ± 0.06%·day-1 , P = 0.99 vs. P: 1.5 ± 0.12 to 2.0 ± 0.15%·day-1 , P = 0.01, ES = 0.97) and (extrapolated) muscle protein breakdown (Z: 93.16 ± 7.8 vs. P: 129.1 ± 13.8 g·day-1 , P = 0.04, ES = 0.92) were reduced with hypogonadism result in lower net protein turnover (3.9 ± 1.1 vs. 1.2 ± 1.1 g·day-1 , P = 0.04, ES = 0.95).CONCLUSIONS: We conclude that endogenous T sufficiency has a central role in the up-regulation of molecular transducers of RET-induced muscle hypertrophy in humans that cannot be overcome by muscle mechano-transduction alone.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Rudrappa, SupreethMRC-Verus Arthritis Centre for Musculoskeletal Ageing Research and Nottingham NIHR BRC, School of Medicine, University of Nottingham, Derby, UK (author)
  • Brook, Matthew SMRC-Verus Arthritis Centre for Musculoskeletal Ageing Research and Nottingham NIHR BRC, School of Medicine, University of Nottingham, Derby, UK (author)
  • Farrash, WesamMRC-Verus Arthritis Centre for Musculoskeletal Ageing Research and Nottingham NIHR BRC, School of Medicine, University of Nottingham, Derby, UK; Laboratory Medicine Department, College of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia (author)
  • Idris, IskandarMRC-Verus Arthritis Centre for Musculoskeletal Ageing Research and Nottingham NIHR BRC, School of Medicine, University of Nottingham, Derby, UK (author)
  • Aziz, Muhammad Hariz AbdulMRC-Verus Arthritis Centre for Musculoskeletal Ageing Research and Nottingham NIHR BRC, School of Medicine, University of Nottingham, Derby, UK (author)
  • Kadi, Fawzi,1970-Örebro universitet,Institutionen för hälsovetenskaper,Division of Sports Sciences, School of Health and Medical Sciences, Örebro University, Örebro, Sweden(Swepub:oru)fki (author)
  • Papaioannou, Konstantinos Georgios,1983-Örebro universitet,Institutionen för hälsovetenskaper,Division of Sports Sciences, School of Health and Medical Sciences, Örebro University, Örebro, Sweden(Swepub:oru)kpu (author)
  • Phillips, Bethan EMRC-Verus Arthritis Centre for Musculoskeletal Ageing Research and Nottingham NIHR BRC, School of Medicine, University of Nottingham, Derby, UK (author)
  • Sian, TanvirMRC-Verus Arthritis Centre for Musculoskeletal Ageing Research and Nottingham NIHR BRC, School of Medicine, University of Nottingham, Derby, UK (author)
  • Herrod, Philip JMRC-Verus Arthritis Centre for Musculoskeletal Ageing Research and Nottingham NIHR BRC, School of Medicine, University of Nottingham, Derby, UK (author)
  • Wilkinson, Daniel JMRC-Verus Arthritis Centre for Musculoskeletal Ageing Research and Nottingham NIHR BRC, School of Medicine, University of Nottingham, Derby, UK (author)
  • Szewczyk, Nathaniel JMRC-Verus Arthritis Centre for Musculoskeletal Ageing Research and Nottingham NIHR BRC, School of Medicine, University of Nottingham, Derby, UK (author)
  • Smith, KennethMRC-Verus Arthritis Centre for Musculoskeletal Ageing Research and Nottingham NIHR BRC, School of Medicine, University of Nottingham, Derby, UK (author)
  • Atherton, Philip JMRC-Verus Arthritis Centre for Musculoskeletal Ageing Research and Nottingham NIHR BRC, School of Medicine, University of Nottingham, Derby, UK (author)
  • MRC-Verus Arthritis Centre for Musculoskeletal Ageing Research and Nottingham NIHR BRC, School of Medicine, University of Nottingham, Derby, UKMRC-Verus Arthritis Centre for Musculoskeletal Ageing Research and Nottingham NIHR BRC, School of Medicine, University of Nottingham, Derby, UK; Laboratory Medicine Department, College of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia (creator_code:org_t)

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  • In:Journal of Cachexia, Sarcopenia and Muscle: John Wiley & Sons13:2, s. 1134-11502190-59912190-6009

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