Postnatal body growth is dependent on the transcription factors signal transducers and activators of transcription 5a/b in muscle: a role for autocrine/paracrine insulin-like growth factor I.
The transcription factors signal transducers and activators of transcription (STAT)5a and STAT5b (STAT5) are essential mediators of many actions of GH, including transcription of the IGF-I gene. Here, we present evidence that skeletal muscle STAT5 is important for postnatal growth and suggest that this is conveyed by the production of localized IGF-I. To investigate the role of STAT5 signaling in skeletal muscle, mice with a skeletal-muscle-specific deletion of the Stat5a and Stat5b genes (Stat5MKO mice) were used. IGF-I mRNA levels were reduced by 60% in muscle tissue of these mice. Despite only a 15% decrease in circulating IGF-I, 8-wk-old male Stat5MKO mice displayed approximately 20% reduction in body weight that was accounted for by a reduction in lean mass. The skeletons of Stat5MKO mice were found to be smaller than controls, indicating the growth defect was not restricted to skeletal muscle. These results demonstrate an as yet unreported critical role for STAT5 in skeletal muscle for local IGF-I production and postnatal growth and suggest the skeletal muscle as a major site of GH action.
Klover
Peter
P
Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 8 Center Drive, Building 8, Room 107, Bethesda, Maryland 20892-0822, USA. kloverp@mail.nih.gov
Hennighausen
Lothar
L
D000818:Animals; D019898:Autocrine Communication; D049628:Body Size / Q000235:genetics; D005260:Female; D006128:Growth / Q000235:genetics*; D013006:Growth Hormone / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism*; D019899:Paracrine Communication; D050799:STAT5 Transcription Factor / Q000235:genetics* / Q000378:metabolism
D050799:STAT5 Transcription Factor; C494093:Stat5a protein, mouse; C494096:Stat5b protein, mouse; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone