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.

Analyses of hind leg skeletons in human growth hormone transgenic rats.

Growth hormone (GH) is essential in the development and growth of the skeleton and for the maintenance of bone mass and density, and its secretion is known to decline with aging. We have previously produced transgenic rats with low circulating GH that represent several age-associated phenotypes such as obesity, insulin-resistance and leptin-resistance. In the present study, the cross-sectional area, bone mineral density, and strength indexes of the hind leg skeletons of the transgenic rats were examined by an X-ray computed tomography scanning. The mean cross-sectional area of the transgenic rats showed no increase after 2 months old up to 8 months old and the strength indexes were significantly lower than their non-transgenic siblings at all ages examined. The trabecular bone mineral density in the transgenic rats drastically decreased at 8 months old, while the cortical bone mineral density was comparable to the non-transgenic rats, suggesting the onset of osteoporosis at this period. The results obtained in this study indicate that the transgenic rats could be useful model to gain insight into the complex mechanism leading to osteoporosis with aging.