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

Growth Horm IGF Res. 2008 Dec;18(6):479-86. doi: 10.1016/j.ghir.2008.04.003. Epub 2008 May 21.

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 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Growth Hormone / genetics
  • Growth Hormone / physiology*
  • Hindlimb / physiology*
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / physiology*
  • Mice
  • Mice, Transgenic
  • Muscle Fibers, Skeletal / physiology*
  • Receptors, Somatotropin / metabolism*

Substances

  • Receptors, Somatotropin
  • growth hormone, bovine
  • Insulin-Like Growth Factor I
  • Growth Hormone