title: Deletion of growth hormone receptors in postnatal skeletal muscle of male mice does not alter muscle mass and response to pathological injury.
abstract: In this study, we investigated whether loss of GH receptor (GHR) signaling in postnatal skeletal muscle alters muscle mass and regenerative ability in adult mice and whether this was dependent on IGF-1 receptor (IGF-1R) signaling. To do so, we used mouse models with skeletal muscle-specific loss of GHR signaling (mGHRKO), IGF-1R and insulin receptor signaling (MKR), or both GHR and IGF-1R/insulin receptor signaling (mGHRKO/MKR). We did not find a reduction in muscle cross-sectional area, fiber type composition, or response to pathological muscle injury in male mGHRKO and mGHRKO/MKR mice when compared with control and MKR mice, respectively. This could potentially be explained by unchanged skeletal muscle Igf-1 expression in mGHRKO and mGHRKO/MKR mice relative to control and MKR mice, respectively. Furthermore, MKR and mGHRKO/MKR mice, but not mGHRKO mice, demonstrated reduced fiber fusion after cardiotoxin injection, suggesting that IGF-1, and not GH, promotes fiber fusion in adult mice. In summary, our data suggest that GHR signaling in postnatal skeletal muscle does not play a significant role in regulating muscle mass or muscle regeneration. Additionally, in our model, muscle Igf-1 expression is not dependent on GHR signaling in postnatal skeletal muscle.
authors.affiliation: MD, PhD, Division of Endocrinology, Metabolism, and Bone Diseases, Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1055, New York, New York 10029. derek.leroith@mssm.edu.
authors.forename: Archana
authors.initials: A
authors.lastname: Vijayakumar
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Buffin
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Gallagher
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Blank
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Wu
authors.forename: Shoshana
authors.initials: S
authors.lastname: Yakar
authors.forename: Derek
authors.initials: D
authors.lastname: LeRoith
mesh_terms: D000818:Animals; D054715:Cardiotoxins / Q000633:toxicity; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000627:therapeutic use; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000235:genetics / Q000378:metabolism*; D012038:Regeneration; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D054715:Cardiotoxins; D007328:Insulin; D011986:Receptors, Somatotropin; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin