Simon Doessing and Michael Kjaer
Institute of Sports Medicine, Department of Orthopaedic Surgery M, Bispebjerg Hospital and Centre for Healthy Aging, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

https://doi.org/10.36866/pn.80.25

Growth hormone and collagen protein

The major role of connective tissue in muscle and tendon is to provide a matrix for the transmission of force from the individual muscle fibres to the bone. Collagen is the primary tensile-resistant protein in musculo-tendinous connective tissue and is a key determinant of tendon strength. In relation to overuse and traumatic muscle and tendon injuries, collagen is inevitably damaged, and recovery depends on the de novo synthesis of collagen. Mechanical loading, as well as several different growth factors, including growth hormone (GH) and insulin-like growth factor-I (IGF-I), appears to have the potential to affect human collagen production. The specific association between the GH/IGF-I system and collagen synthesis is most evident in patients with acromegaly, where long-term elevated GH nd IGF-I levels cause excessive growth of collagen tissues, including skin, bone and cartilage. In normo endocrine individuals GH supplementation is positively associated with collagen synthesis based on indirect whole-body measurements, and in vitro animal studies show that IGF-I increases tendon fibroblast collagen production. We recently observed that just 14 days of GH supplementation increased collagen expression and collagen synthesis – up to 6-fold – in skeletal muscle and tendon in healthy human adults (Doessing et al. 2010). Moreover, in a recent (unpublished) study we observed a similar association between circulating GH/IGF-I and local musculo-tendinous collagen production in acromegalic and growth hormone-deficient (GHD) patients.

Growth hormone and skeletal muscle contractile/myofibrillar protein

The effect of GH on human muscle size/strength and contractile myofibrillar protein synthesis is a matter of controversy. While there is little doubt that GH/IGF-I increases muscle strength and contractive muscle protein synthesis in growing animals (Shavlakadze et al. 2010), a similar role for GH in skeletal muscle of adult normo-endocrine individuals is less evident. In our hands, there was no effect on contractile/myofibrillar protein synthesis of short-term GH supplementation in healthy human adults or of long-term alterations in GH titre in acromegalic and GHD patients. These observations are in concert with most previous human experiments where no effect on muscle strength and myofibrillar protein synthesis is observed.

Locally produced IGF-I as a potential paracrine/autocrine regulator of protein synthesis

The role of liver-derived circulating IGF-I as a primary peripheral mediator of GH actions is debated. Abolishment of hepatocyte IGF-I production has no effect on growth in mice, and it is suggested that systemic IGF-I primarily functions as a negative feedback regulator of pituitary GH synthesis. In contrast, locally produced IGF-I seems important in the regulation of local protein synthesis, including collagen. We observed that the expression of local IGF-I isoforms was up-regulated in GH-supplemented individuals (Doessing et al. 2010) as well as in acromegalic patients. Importantly, local IGF-I expression was closely associated with local collagen expression in both studies. This suggests that locally produced IGF-I could mediate the effect of GH on tissue protein synthesis in an autocrine/paracrine manner.

Doping with growth hormone

Doping with recombinant human (rh) GH and rhIGF-I is a widespread problem within a range of sports, from amateurs to professionals. GH and IGF-I are both on the World Anti-Doping Agency (WADA) list of banned substances and according to the 2007 Donati/WADA report it is estimated that more than 5 million people abuse rhGH worldwide. Anecdotal evidence suggests that GH is abused as doping by athletes partly due to its muscle anabolic properties. It is therefore a paradox that studies investigating the effect of GH supplementation on human adults show no effect of GH on muscle strength and contractile muscle protein synthesis. Interestingly, it is speculated by athletes, particularly within the bodybuilding community, that GH doping can prevent acute muscle and tendon injuries. Muscle and tendon ruptures are a common complication to heavy-weight training in combination with anabolic steroid abuse, and finding ways to strengthen the collagen connective tissue and thus decrease the risk of injury seems highly advantageous. As one bodybuilder described his GH experience: ‘GH is probably the most remarkable drug at increasing collagen synthesis. It increases collagen synthesis in a dose dependant manner’ (www. steroidology.com).

Interestingly, in a recent study on recreational athletes it has been shown that GH did not increase muscle mass but increased sprint performance when GH was administered alone or in combination with testosterone (Meinhardt et al. 2010). This finding is in accordance with the view that improved collagen formation after GH administration causes a more efficient force transmission in human skeletal muscle.

Does GH/IGF-I have a potential in the treatment of muscle and tendon injury?

The rumoured ‘injury-preventing effect’ of GH doping fits well with the observed effect of GH on collagen connective tissue observed in controlled experiments. It is therefore relevant to speculate whether GH has a potential in the treatment of over-use or acute muscle and tendon injuries. However, no studies have investigated the treatment potential of GH or IGF-I supplementation in relation to acute- or over-use muscle/tendon injuries in man.

References

Doessing S, Heinemeier KM, Holm L, Mackey AL, Schjerling P, Rennie M, Smith K, Reitelseder S, Kappelgaard AM, Rasmussen MH, Flyvbjerg A & Kjaer M (2010). Growth hormone stimulates the collagen synthesis in human tendon and skeletal muscle without affecting myofibrillar protein synthesis. J Physiol 588, 341–351. http://jp.physoc.org/content/588/2/341.long

Meinhardt U, Nelson AE, Hansen JL, Birzniece V, Clifford D, Leung KC, Graham K & Ho KK (2010). The effects of growth hormone on body composition and physical performance in recreational athletes: a randomized trial. Ann Intern Med 152, 568–577.

Shavlakadze T, Chai J, Maley K, Cozens G, Grounds G, Winn N, Rosenthal N & Grounds MD (2010). A growth stimulus is needed for IGF-1 to induce skeletal muscle hypertrophy in vivo. J Cell Sci 123, 960–971.