Skeletal muscle growth defect in human growth hormone transgenic rat is accompanied by phenotypic changes in progenitor cells.
Growth hormone (GH) is known to have a pivotal role in the maintenance of skeletal muscle mass. Sarcopenia, the loss of skeletal muscle mass, is a common phenomenon in aging, and it is widely accepted that sarcopenia is largely attributed to age-related decline in GH secretion. In the present study, we tested if human growth hormone transgenic rats (GH-TG rats) whose plasma GH levels are maintained relatively low could be an appropriate model for sarcopenia. Analyses of GH-TG rats revealed that they exhibit skeletal muscle growth defect as well as atrophy of myofibers. The number of myofibers in tibialis anterior muscle was comparable to that of WT rats, while the proportion of type I slow myofibers in tibialis anterior muscle was increased in GH-TG rats after 5 months. Neither increased expression of ubiquitin ligases, MuRF1 and MAFbx, nor indication of apoptotic cell death was observed. Notably, myogenic differentiation potential of skeletal muscle progenitor cells in GH-TG rats was lower than WT rats, and this was accompanied by increased adipogenic potential. These results indicate that GH-TG rats could be a useful model to elucidate the mechanism of sarcopenia induced by reduced GH action and raised the possibility that decreased GH action may cause an alteration of differentiation potential of skeletal muscle progenitor cells.
Shibata
Shingo
S
Department of Veterinary Physiology, The University of Tokyo, 1-1-1 Yayoi, Bunkyo, Tokyo 113-8657, Japan.
Ueno
Chiori
C
Ito
Tsuyoshi
T
Yamanouchi
Keitaro
K
Matsuwaki
Takashi
T
Nishihara
Masugi
M
D000367:Age Factors; D000375:Aging; D000818:Animals; D015152:Blotting, Northern; D002454:Cell Differentiation; D013006:Growth Hormone / Q000172:deficiency; D007150:Immunohistochemistry; D018482:Muscle, Skeletal / Q000254:growth & development* / Q000473:pathology / Q000503:physiopathology*; D010641:Phenotype; D051381:Rats; D055647:Rats, Transgenic; D055948:Sarcopenia / Q000473:pathology / Q000503:physiopathology; D013234:Stem Cells / Q000502:physiology*
D013006:Growth Hormone