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


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.


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.
Doessing
Simon
S
Department of Orthopaedic Surgery M, Faculty of Health Sciences, Institute of Sports Medicine, Bispebjerg Hospital and Centre for Healthy Aging, University of Copenhagen, Bispebjerg Bakke 23, Copenhagen DK-2400, Denmark. simondoessing@gmail.com
Holm
Lars
L
Heinemeier
Katja M
KM
Feldt-Rasmussen
Ulla
U
Schjerling
Peter
P
Qvortrup
Klaus
K
Larsen
Jytte O
JO
Nielsen
Rie H
RH
Flyvbjerg
Allan
A
Kjaer
Michael
M
D000328:Adult; D003094:Collagen / Q000096:biosynthesis*; D024042:Collagen Type I / Q000096:biosynthesis; D024061:Collagen Type III / Q000096:biosynthesis; D019382:Human Growth Hormone / Q000172:deficiency* / Q000378:metabolism*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013710:Tendons / Q000378:metabolism* / Q000648:ultrastructure
D024042:Collagen Type I; D024061:Collagen Type III; D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D003094:Collagen