GH and IGF1 levels are positively associated with musculotendinous collagen expression: experiments in acromegalic and GH deficiency patients

Abstract

Objective: Disproportionate growth of musculoskeletal tissue is a major cause of morbidity in both acromegalic (ACRO) and GH-deficient (GHD) patients. GH/IGF1 is likely to play an important role in the regulation of tendon and muscle collagen. We hypothesized that the local production of collagen is associated with the level of GH/IGF1. Design and methods: As primary outcomes, collagen mRNA expression and collagen protein fractional synthesis rate (FSR) were determined locally in skeletal muscle and tendon in nine ACRO and nine GHD patients. Moreover, muscle myofibrillar protein synthesis and tendon collagen morphology were determined. Results and conclusions: Muscle collagen I and III mRNA expression was higher in ACRO patients versus GHD patients (P!0.05), whereas collagen protein FSR did not differ significantly between ACRO and GHD patients in muscle (PZ0.21) and tendon (PZ0.15). IGF1Ea and IGF1Ec mRNA expression in muscle was higher in ACRO patients versus GHD patients (P!0.01). Muscle IGF1Ea mRNA expression correlated positively with collagen I mRNA expression (P!0.01). Tendon collagen fibrillar area tended to be higher in GHD patients relative to ACRO patients (PZ0.07). Thus, we observed a higher expression for collagen and IGF1 mRNA in local musculotendinous tissue in ACRO patients relative to GHD patients. Moreover, there was a tendency towards a higher collagen protein FSR and a smaller collagen fibril diameter in ACRO patients relative to GHD patients. The results indicate a collagenstimulating role of local IGF1 in human connective tissue and add to the understanding of musculoskeletal pathology in patients with either high or low GH/IGF1 axis activity.

Structural tendon changes in patients with acromegaly: assessment of Achilles tendon with sonoelastography.

“…They found a tendency toward a smaller tendon collagen fibril area and a higher concentration of small collagen fibrils in acromegalic patients than in GH-deficient patients. This finding suggests that a chronically high level of GH/IGF1, with a concomitant increase in collagen expression and in absolute collagen synthesis, correlates with a smaller collagen fibril area in the tendon [17].…”

“…A doubling of GH and IGF-I levels did not change the collagen fibril volume fraction, but it did affect the diameter distribution as it presented more small fibrils than in the control mice [16]. In the second study, Doessing et al found quantitative collagen morphology in the tendons of acromegaly patients [17]. They found a tendency toward a smaller tendon collagen fibril area and a higher concentration of small collagen fibrils in acromegalic patients than in GH-deficient patients.…”

Therapeutic use of hormones on tendinopathies: a narrative review

“…In a study the collagen mRNA expression and collagen protein fractional synthesis rate (FSR) was evaluated locally, in muscles and tendons, by means of microdialysis technique, in acromegalics, relative to GH deficient patients 34 . A higher expression for collagen and IGF1 mRNA was found in acromegalics.…”

Biologic and Tissue Engineering Strategies for Tendon Repair

“…GH increases IGF-1 expression; acromegalic patients (who produce excess GH), for example, display a 2.9-fold increase in IGF-1 expression relative to GH-deficient patients. Musculotendinous collagen expression was elevated 1.7-fold in these patients, which the authors attribute to this excess IGF-1 production [45]. Doessing et al demonstrated that subcutaneous GH injections (at dosages between 33.3 and 50 μg/kg/day for 14 days) increased tendon Col-1 expression in healthy human patients 3.9-fold [46].…”