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Effects of growth hormone (GH) disruption on muscle fiber type composition in mouse hindlimb

Posted on:2007-09-21Degree:Ph.DType:Dissertation
University:Ohio UniversityCandidate:Schuenke, Mark DFull Text:PDF
GTID:1443390005469823Subject:Biology
Abstract/Summary:
To date, the effects of growth hormone (GH) on muscle fiber phenotype have not been clearly elucidated. Studies employing hypophysectomy have been confounded by the loss of not only GH but other hormones produced by the anterior pituitary gland, whereas studies using GH supplementation have produced erratic results. Purpose. To investigate the effects of GH and insulin-like growth factor-I (IGF-I) on fiber type composition of selected mouse hindlimb muscles. Methods. The triceps surae muscle group was harvested from mice that were either: (1) giant due to expression of a bovine GH transgene (bGH) that resulted in high levels of serum IGF-I, (2) dwarf due to the disruption of the GHR/binding protein gene (GHR-/-) that resulted in low levels of serum IGF-1, or (3) normal-sized [nontransgenic (NT)] controls. Serial cross sections were assayed for mATPase activity and used to delineate eight fiber types (1, IC, IIC, IIA, IIAD, IID, IIDB, and IIB). Cross-sectional areas were subsequently determined on ∼50 fibers/type. Results. Muscles from bGH mice demonstrated a significantly (P<0.05) higher percentage of the slow fiber phenotype compared to NT control littermates. Also, significantly larger cross-sectional areas of most fiber types (primarily confined to the most oxidative fiber types) were found in the bGH mice. In contrast, fiber phenotype in GHR-/- mice did not differ significantly from NT mice. However, significant reductions were found in the size of all muscle fiber types. Regardless of mouse genotype and phenotype, the hierarchy of fiber size was maintained such that type I fibers were the largest in soleus, whereas, type IIB fibers were the largest in plantaris, the superficial white portion of the gastrocnemius, and the deep red portion of the gastrocnemius. Conclusions. The results suggest that GH has a profound and divergent effect on muscle phenotype both directly (independent of IGF-I) and indirectly (via IGF-I mediating mechanisms).
Keywords/Search Tags:Muscle, Fiber, Type, Growth, Effects, IGF-I, Mouse
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