The Effect of Growth Hormone Receptor Deficiency on Skeletal Muscle Insulin-like Growth Factor-I Protein Expression

Abstract

PURPOSE: Growth hormone (GH) is a potent secretague for circulating insulin-like growth factor-IEa (IGF-IEa). The purpose of this study was to examine the effect of circulating GH on muscle IGF-IEa protein expression using GH transgenic animal models. METHODS: Three different models were used: mice that overexpress bovine GH (bGH; n=10), mice without a functional GH receptor (GHR-/-; n=10), and wildtype mice (n=10). All mice were 16-week old females and each group differed in their basic phenotypic characteristics. Immediately after euthanization the triceps surae muscle group (soleus, plantaris, and gastrocnemius muscles) was removed. The IGF-IEa was extracted from the muscle with and acid-ethanol solution (12.5 % 2N hydrochloric acid and 87.5 % ethanol, pH 1.5) followed by neutralization with Tris-base and subsequently quantified using a radioimmunoassay. RESULTS: Analysis revealed that bGH had significantly greater IGF-IEa protein expression compared to GHR-/-and wildtype mice. No difference in IGF-IEa protein concentration was found between GHR-/-and wildtype animals. This study found that overexpression of GH leading to high circulating GH concentrations increase muscle IGF-IEa protein expression. However, the absence of a functional GH receptor did not affect muscle IGF-IEa protein expression compared to wildtype despite high circulating levels of GH and low circulating levels of IGF-IEa. CONCLUSIONS: In conclusion, it appears that at rest high circulating concentrations of GH augment muscle IGF-IEa protein expression only in the presence of an intact GH receptor but that the absence of a functional GH receptor does not affect basal concentrations of muscle IGF-IEa protein in female mice.