Skeletal Muscle Performance in Adults with Growth Hormone Deficiency

Cuneo, Ross C.; Salomon, Franco; Wiles, C M; Sönksen, Peter H.

doi:10.1159/000181585

Cited by 132 publications

(67 citation statements)

References 19 publications

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“…This is consistent with the lipolytic and anabolic effects of GH observed in previous studies (4,10,23,24), demonstrating that a moderate dose of GH can induce a sustained improvement in body composition in elderly GHD adults. GH replacement, as previously shown (10,25), had a more marked effect on isometric knee flexor strength than on isokinetic knee flexor strength, possibly as a consequence of more reduced isometric strength in untreated GHD adults (9,26). This allows to assume that increased muscle strength during GH replacement is not only due to increased muscle mass (27)(28)(29).…”

Section: Discussionmentioning

confidence: 60%

Muscle strength in elderly adults with GH deficiency after 10 years of GH replacement

Götherström¹,

Elbornsson²,

Sunnerhagen³

et al. 2010

European Journal of Endocrinology

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Context: Only few studies have investigated the effects of GH replacement on muscle strength in elderly patients with GH deficiency (GHD). Objective, design, and patients: In this prospective open-labeled study, the effects of 10 years of GH replacement on muscle strength and neuromuscular function were followed in 24 elderly GHD adults (mean age of 65.2 years; range 61-74 years). Muscle strength was compared with reference values obtained from the background population. Results: The mean initial GH dose of 0.72 mg/day was lowered to 0.37 mg/day. The mean IGF1 SDS increased from K1.10 at baseline to 1.17 at study end. GH replacement induced a sustained increase in lean body mass and a transient increase in isometric knee flexor strength. Isometric knee extensor strength was reduced after 10 years. However, after correction for age and gender, using observed/predicted value ratios, there was sustained and even progressive increase in most variables reflecting muscle strength. Measurements of neuromuscular function showed unchanged voluntary motor unit activation after 10 years. Conclusions: Ten years of GH replacement therapy in elderly GHD adults resulted in a transient increase in isometric knee flexor strength, and provided protection from most of the normal age-related decline in muscle performance and neuromuscular function.

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Section: Discussionmentioning

confidence: 60%

Muscle strength in elderly adults with GH deficiency after 10 years of GH replacement

Götherström¹,

Elbornsson²,

Sunnerhagen³

et al. 2010

European Journal of Endocrinology

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“…Low muscle quality was possibly linked to the deficiency in growth hormone and, consequently, secondary deficiency in circulating insulin‐like growth factor 1 (IGF‐1)/insulin signaling. Muscle strength associates with genetic variation in IGF1 in individuals, and patients with disrupted growth hormone/IGF‐1/insulin signaling tend to exhibit diminished muscle quality (Cuneo & Wallace, 2005; Cuneo, Salomon, Wiles, & Sonksen, 1990; Huuskonen et al, 2011). …”

Section: Discussionmentioning

confidence: 99%

VCAM‐1 upregulation accompanies muscle remodeling following resistance‐type exercise in Snell dwarf (Pit1^dw/dw) mice

et al. 2018

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Snell dwarf mice (Pit1dw/dw) exhibit deficiencies in growth hormone, prolactin, and thyroid stimulating hormone. Besides being an experimental model of hypopituitarism, these mice are long‐lived (>40% lifespan extension) and utilized as a model of slowed/delayed aging. Whether this longevity is accompanied by a compromised quality of life in terms of muscular performance has not yet been characterized. In this study, we investigated nontrained and trained muscles 1 month following a general validated resistance‐type exercise protocol in 3‐month‐old Snell dwarf mice and control littermates. Nontrained Snell dwarf gastrocnemius muscles exhibited a 1.3‐fold greater muscle mass to body weight ratio than control values although muscle quality, maximum isometric torque normalized to muscle mass, and fatigue recovery were compromised. For control mice, training increased isometric torque (17%) without altering muscle mass. For Snell dwarf mice, isometric torque was unaltered by training despite decreased muscle mass that rendered muscle mass to body weight ratio comparable to control values. Muscle quality and fatigue recovery improved twofold and threefold, respectively, for Snell dwarf mice. This accompanied a fourfold increase in levels of vascular cell adhesion molecule‐1 (VCAM‐1), a mediator of progenitor cell recruitment, and muscle remodeling in the form of increased number of central nuclei, additional muscle fibers per unit area, and altered fiber type distribution. These results reveal a trade‐off between muscle quality and longevity in the context of anterior pituitary hormone deficiency and that resistance‐type training can diminish this trade‐off by improving muscle quality concomitant with VCAM‐1 upregulation and muscle remodeling.

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“…GH is one of the most important factors that regulates postnatal longitudinal growth, body weight, and body composition in mammals (18,(41)(42)(43)(44)(45). GH exerts anabolic actions in skeletal muscle by both promoting muscle development and facilitating nutrient uptake and utilization in the muscle, thereby coordinating global energy expenditure and body composition (46,47).…”

Section: Discussionmentioning

confidence: 99%

Distinct growth hormone receptor signaling modes regulate skeletal muscle development and insulin sensitivity in mice

Mavalli¹,

DiGirolamo²,

Fan³

et al. 2010

J. Clin. Invest.

180

138

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Skeletal muscle development, nutrient uptake, and nutrient utilization is largely coordinated by growth hormone (GH) and its downstream effectors, in particular, IGF-1. However, it is not clear which effects of GH on skeletal muscle are direct and which are secondary to GH-induced IGF-1 expression. Thus, we generated mice lacking either GH receptor (GHR) or IGF-1 receptor (IGF-1R) specifically in skeletal muscle. Both exhibited impaired skeletal muscle development characterized by reductions in myofiber number and area as well as accompanying deficiencies in functional performance. Defective skeletal muscle development, in both GHR and IGF-1R mutants, was attributable to diminished myoblast fusion and associated with compromised nuclear factor of activated T cells import and activity. Strikingly, mice lacking GHR developed metabolic features that were not observed in the IGF-1R mutants, including marked peripheral adiposity, insulin resistance, and glucose intolerance. Insulin resistance in GHR-deficient myotubes derived from reduced IR protein abundance and increased inhibitory phosphorylation of IRS-1 on Ser 1101. These results identify distinct signaling pathways through which GHR regulates skeletal muscle development and modulates nutrient metabolism. IntroductionMammalian skeletal muscle has evolved to perform a diverse set of functions, including locomotion, breathing, protecting internal organs, and coordinating global energy expenditure. Skeletal muscle is formed and regenerated through a highly regulated process characterized by myoblast differentiation and fusion into multinucleated syncytia. During embryonic development, specification of mesodermal precursor cells into the myogenic lineage is controlled by signals from surrounding tissues and requires upregulation of several factors, including paired-box transcription factor 7 (pax-7) and basic helix-loop-helix transcriptional activators of the myogenic regulatory factor family, MyoD and Myf-5 (1). The proliferating precursor cells/myoblasts withdraw from the cell cycle and initiate muscle-specific gene expression (2, 3). Myoblasts then initially fuse to form nascent myotubes, with relatively few nuclei, through a highly ordered set of cellular events, including recognition, adhesion, alignment, and membrane union. Subsequent recruitment and fusion of additional myoblasts gives rise to multinucleated myotubes that ultimately mature to give rise to skeletal muscle fibers. The fusion process is controlled, in part, by the actions of calcium-sensitive transcription factors of the nuclear factor of activated T cells (NFAT) family (4, 5). During myoblast fusion,

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Skeletal Muscle Performance in Adults with Growth Hormone Deficiency

Cited by 132 publications

References 19 publications

Muscle strength in elderly adults with GH deficiency after 10 years of GH replacement

Muscle strength in elderly adults with GH deficiency after 10 years of GH replacement

VCAM‐1 upregulation accompanies muscle remodeling following resistance‐type exercise in Snell dwarf (Pit1^dw/dw) mice

Distinct growth hormone receptor signaling modes regulate skeletal muscle development and insulin sensitivity in mice

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Skeletal Muscle Performance in Adults with Growth Hormone Deficiency

Cited by 132 publications

References 19 publications

Muscle strength in elderly adults with GH deficiency after 10 years of GH replacement

Muscle strength in elderly adults with GH deficiency after 10 years of GH replacement

VCAM‐1 upregulation accompanies muscle remodeling following resistance‐type exercise in Snell dwarf (Pit1dw/dw) mice

Distinct growth hormone receptor signaling modes regulate skeletal muscle development and insulin sensitivity in mice

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VCAM‐1 upregulation accompanies muscle remodeling following resistance‐type exercise in Snell dwarf (Pit1^dw/dw) mice