|Titel på arbejdet
|Activation of the GH and IGF-I axis increases collagen synthesis in human tendon and skeletal muscle
|Afdeling / Sted
|Institute of Sports Medicine Copenhagen
|Abstract / Summary
Collagen is the most abundant protein in the body and the main tensile bearing protein of the connective tissue in skeletal muscle and tendon. Stimulation of connective tissue by mechanical loading can elicit an increase in collagen synthesis of both human and animal tendon/muscle, as well as an increase in insulin-like growth factor-I (IGF-I) expression in tendon of animals. This suggests a link between growth hormone (GH)/IGF-I and collagen synthesis. Accordingly, in patients with acromegaly (with elevated GH levels) and in growth hormone deficient patients (GHD), there is a positive association between GH/IGF-I and growth of collagen tissue. Moreover, in both patient groups, circulating GH and IGF-I are positively associated with the level of circulating collagen pro-peptides. In agreement with this, short-term GH supplementation increases circulating collagen pro-peptides in healthy human adults. Although such findings indirectly suggest that GH/IGF-I is involved in the regulation of collagen, they do not directly demonstrate any coupling between IGF-I and collagen synthesis, and neither do they specify in which tissue a stimulation of collagen synthesis takes place. In contrast to the possible effect of GH/IGF-I on collagen synthesis, myofibrillar protein synthesis and muscle mass appear to be unaffected by GH in supra-physiological levels, as observed in acromegalic patients and in healthy human adults supplemented with GH. The primary aim of this project was to investigate the effect of altered levels of circulating GH/IGF- I on local collagen and myofibrillar protein synthesis in human tendon and skeletal muscle. Moreover, we studied the possible correlation between the local expression of collagen and local/systemic IGF-I. As secondary aim we studied the combined effect of exercise and GH/IGF-I on collagen and myofibrillar protein synthesis. We examined patients with acromegaly and GHD, as well as healthy human participants following short-term GH supplementation. We found that the level of circulating GH/IGF-I was positively associated with the local expression of both IGF-I and collagen mRNA. Moreover, circulating GH/IGF-I was positively associated with collagen protein synthesis rate in both tendon and skeletal muscle. Local IGF-I mRNA expression correlated significantly to local collagen mRNA expression. In contrast to the effect of GH/IGF-I on collagen expression and synthesis, myofibrillar protein synthesis rate was not affected by GH/IGF-I. The effect of GH on collagen protein synthesis was also evident during exercise, but there was no effect of exercise per se on collagen or myofibrillar protein synthesis.