title: Lack of contribution of 11betaHSD1 and glucocorticoid action to reduced muscle mass associated with reduced growth hormone action.
abstract: 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.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Virginia, Box 800466, Charlottesville, VA 22908, USA.
authors.forename: Emina
authors.initials: E
authors.lastname: Itoh
authors.forename: Keiji
authors.initials: K
authors.lastname: Iida
authors.forename: Dong-Sun
authors.initials: DS
authors.lastname: Kim
authors.forename: Juan P
authors.initials: JP
authors.lastname: Del Rincon
authors.forename: Karen T
authors.initials: KT
authors.lastname: Coschigano
authors.forename: John J
authors.initials: JJ
authors.lastname: Kopchick
authors.forename: Michael O
authors.initials: MO
authors.lastname: Thorner
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000235:genetics; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000378:metabolism*; D005974:Glutamate-Ammonia Ligase / Q000235:genetics / Q000378:metabolism; D013006:Growth Hormone / Q000172:deficiency / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D018482:Muscle, Skeletal / Q000502:physiology / Q000503:physiopathology*; D009133:Muscular Atrophy / Q000209:etiology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000235:genetics / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D042842:11-beta-Hydroxysteroid Dehydrogenases; D005974:Glutamate-Ammonia Ligase