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Publication : Lack of contribution of 11betaHSD1 and glucocorticoid action to reduced muscle mass associated with reduced growth hormone action.

First Author  Itoh E Year  2004
Journal  Growth Horm IGF Res Volume  14
Issue  6 Pages  462-6
PubMed ID  15519255 Mgi Jnum  J:101921
Mgi Id  MGI:3605925 Doi  10.1016/j.ghir.2004.07.002
Citation  Itoh E, et al. (2004) Lack of contribution of 11betaHSD1 and glucocorticoid action to reduced muscle mass associated with reduced growth hormone action. Growth Horm IGF Res 14(6):462-6
abstractText  11Beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) is expressed in several tissues and converts inactive glucocorticoids (GC) to active GC. 11betaHSD1 activity, evaluated by urine cortisol metabolites, is increased in patients with hypopituitarism and decreased by GH replacement. Skeletal muscle wasting is one of the major characteristics of GH deficiency (GHD). We hypothesized that increased 11betaHSD1 activity and increased GC action in skeletal muscle may play a role in the development of muscle atrophy observed in GHD patients. Glutamine synthetase (GS) mRNA in muscle has been reported to be related to GC-induced muscle atrophy. In this study, we measured mRNA levels of 11betaHSD1 and GS in skeletal muscle of GH receptor gene disrupted (GHR-/-) mice and of their age-matched wild-type mice controls to elucidate the physiological significance of 11betaHSD1 and GC in the development of GHD-associated muscle atrophy in vivo. We also measured the expression of these genes in hypertrophied muscles of giant, bovine GH transgenic mice. In skeletal muscle, although IGF-I mRNA levels were decreased in GHR-/- mice, 11betaHSD1 mRNA levels were not significantly changed compared to wild-type mice. In addition, expression level of 11betaHSD1 in muscle was lower compared to that seen in liver. GS mRNA in skeletal muscle of GHR-/- mice was not significantly different from that of controls. In bGH mice, 11betaHSD1 and GS mRNA levels were not altered compared to control mice. These data do not support a significant role of 11betaHSD1 and GC action in skeletal muscle in the development of muscle atrophy associated with GHD.
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