This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gilson, H. Articles by Thissen, J. P. Search for Related Content PubMed PubMed Citation Articles by Gilson, H. Articles by Thissen, J. P.

Myostatin Gene Deletion Prevents Glucocorticoid-Induced Muscle Atrophy

Unité de Diabétologie et Nutrition (H.G., O.S., P.L., J.M.K., J.P.T.), Université Catholique de Louvain, B-1200 Brussels, Belgium; Unité d’Embryologie, Faculté de Médecine Vétérinaire (L.G.), Université de Liège, B-4000 Liège, Belgium; and Human Nutrition Unit (L.C., D.A.), Human Nutrition Research Centre of Clermont-Ferrand, Unité Mixte de Recherche 1019 Institut National de la Recherche Agronomique, 63122 Ceyrat, France

Address all correspondence and requests for reprints to: Jean-Paul Thissen, Unité de Diabétologie et Nutrition, Université Catholique de Louvain, 54 avenue Hippocrate, B-1200 Brussels, Belgium. E-mail: thissen{at}diab.ucl.ac.be.

Glucocorticoids mediate muscle atrophy in many catabolic states. Myostatin expression, a negative regulator of muscle growth, is increased by glucocorticoids and myostatin overexpression is associated with lower muscle mass. This suggests that myostatin is required for the catabolic effects of glucocorticoids. We therefore investigated whether myostatin gene disruption could prevent muscle atrophy caused by glucocorticoids. Male myostatin knockout (KO) and wild-type mice were subjected to dexamethasone treatment (1 mg/kg·d for 10 d or 5 mg/kg·d for 4 d). In wild-type mice, daily administration of low-dose dexamethasone for 10 d resulted in muscle atrophy (tibialis anterior: –15%; gastrocnemius: –13%; P < 0.01) due to 15% decrease in the muscle fiber cross-sectional area (1621 ± 31 vs. 1918 ± 64 µm², P < 0.01). In KO mice, there was no reduction of muscle mass nor fiber cross-sectional area after dexamethasone treatment. Muscle atrophy after 4 d of high-dose dexamethasone was associated with increased mRNA of enzymes involved in proteolytic pathways (atrogin-1, muscle ring finger 1, and cathepsin L) and increased chymotrypsin-like proteasomal activity. In contrast, the mRNA of these enzymes and the proteasomal activity were not significantly affected by dexamethasone in KO mice. Muscle IGF-I mRNA was paradoxically decreased in KO mice (–35%, P < 0.05); this was associated with a potentially compensatory increase of IGF-II expression in both saline and dexamethasone-treated KO mice (2-fold, P < 0.01). In conclusion, our results show that myostatin deletion prevents muscle atrophy in glucocorticoid-treated mice, by blunting the glucocorticoid-induced enhanced proteolysis, and suggest an important role of myostatin in muscle atrophy caused by glucocorticoids.

This article has been cited by other articles:

				L. Carraro, S. Ferraresso, B. Cardazzo, C. Romualdi, C. Montesissa, F. Gottardo, T. Patarnello, M. Castagnaro, and L. Bargelloni Expression profiling of skeletal muscle in young bulls treated with steroidal growth promoters Physiol Genomics, July 1, 2009; 38(2): 138 - 148. [Abstract] [Full Text] [PDF]

				M. J. Tisdale Mechanisms of Cancer Cachexia Physiol Rev, April 1, 2009; 89(2): 381 - 410. [Abstract] [Full Text] [PDF]

				M. S. Willis, M. Rojas, L. Li, C. H. Selzman, R.-H. Tang, W. E. Stansfield, J. E. Rodriguez, D. J. Glass, and C. Patterson Muscle ring finger 1 mediates cardiac atrophy in vivo Am J Physiol Heart Circ Physiol, April 1, 2009; 296(4): H997 - H1006. [Abstract] [Full Text] [PDF]

				A. Amirouche, A.-C. Durieux, S. Banzet, N. Koulmann, R. Bonnefoy, C. Mouret, X. Bigard, A. Peinnequin, and D. Freyssenet Down-Regulation of Akt/Mammalian Target of Rapamycin Signaling Pathway in Response to Myostatin Overexpression in Skeletal Muscle Endocrinology, January 1, 2009; 150(1): 286 - 294. [Abstract] [Full Text] [PDF]

				F. J. Lopez, R. J. Ardecky, B. Bebo, K. Benbatoul, L. De Grandpre, S. Liu, M. D. Leibowitz, K. Marschke, J. Rosen, D. Rungta, et al. LGD-5552, an Antiinflammatory Glucocorticoid Receptor Ligand with Reduced Side Effects, in Vivo Endocrinology, May 1, 2008; 149(5): 2080 - 2089. [Abstract] [Full Text] [PDF]

				O Schakman, H Gilson, and J P Thissen Mechanisms of glucocorticoid-induced myopathy J. Endocrinol., April 1, 2008; 197(1): 1 - 10. [Abstract] [Full Text] [PDF]

				R. A. Frost and C. H. Lang Protein kinase B/Akt: a nexus of growth factor and cytokine signaling in determining muscle mass J Appl Physiol, July 1, 2007; 103(1): 378 - 387. [Abstract] [Full Text] [PDF]