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

Abstract

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 ∼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.