Effects of growth hormone overexpression vs. growth hormone receptor gene disruption on mouse hindlimb muscle fiber type composition.

OBJECTIVE: The present study characterizes the fiber type composition of selected hindlimb muscles from two transgenic mouse lines specifically engineered to alter the amounts of circulating growth hormone (GH) and insulin-like growth factor-1 (IFG-1).
DESIGN: The triceps surae muscle group (soleus m., gastrocnemius m., and plantaris m.) was harvested en masse from mice that were: (1) giant due to the expression of a bovine GH transgene (bGH), (2) dwarf due to the disruption of the GH receptor/binding protein gene (GHR-/-), and (3) normal-sized controls [non-transgenic (NT)]. Histochemical and immunohistochemical methods were utilized on serial cross sections to delineate eight fiber types (I, IC, IIC, IIA, IIAD, IID, IIDB, and IIB). Cross-sectional areas were subsequently determined on approximately 50 fibers/type.
RESULTS: Compared to NT littermates, muscles from bGH mice demonstrated a significant (p<0.05) fast-to-slow shift in fiber phenotype, as well as significantly larger fibers for most types. In contrast, significantly smaller fibers were found for all fiber types in the GHR-/- mice, with no significant differences in fiber type percentages compared to NT. Regardless of mouse genotype, the hierarchy of fiber size was maintained in each muscle with type I the largest in the soleus m. and type IIB the largest in the predominantly fast muscles (plantaris, superficial and deep gastrocnemius muscles).
CONCLUSION: In conclusion, the genetic manipulation of GH expression (bGH) and its receptor binding (GHR-/-) had profound and divergent effects on muscle phenotype. It is hoped that continued research in this area will help elucidate the direct (independent of IGF-1) vs. indirect (via IGF-1 mediating mechanisms) effects of GH.