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

TY - JOUR

T1 - GH and IGF1 levels are positively associated with musculotendinous collagen expression: experiments in acromegalic and GH deficiency patients

AU - Doessing, Simon

AU - Holm, Lars

AU - Heinemeier, Katja M

AU - Feldt-Rasmussen, Ulla

AU - Schjerling, Peter

AU - Qvortrup, Klaus

AU - Larsen, Jytte O

AU - Nielsen, Rie H

AU - Flyvbjerg, Allan

AU - Kjaer, Michael

PY - 2010/12/1

Y1 - 2010/12/1

N2 - 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 (P=0.21) and tendon (P=0.15). 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 (P=0.07). 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 collagen-stimulating 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.

AB - 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 (P=0.21) and tendon (P=0.15). 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 (P=0.07). 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 collagen-stimulating 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.

KW - Adult

KW - Collagen

KW - Collagen Type I

KW - Collagen Type III

KW - Human Growth Hormone

KW - Humans

KW - Insulin-Like Growth Factor Binding Protein 3

KW - Insulin-Like Growth Factor I

KW - Male

KW - Microscopy, Electron, Transmission

KW - Middle Aged

KW - Muscle, Skeletal

KW - RNA, Messenger

KW - Tendons

U2 - 10.1530/EJE-10-0818

DO - 10.1530/EJE-10-0818

M3 - Journal article

C2 - 20858702

SN - 0804-4643

VL - 163

SP - 853

EP - 862

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

IS - 6

ER -