Inhibition of the phosphotidylinositol 3‐kinase (PI3K) pathway attenuates post‐exercise increases in soleus muscle satellite cells in estrogen supplemented ovariectomized rats

Abstract

17β‐Estradiol (E2) enhances the activation, proliferation and differentiation of muscle satellite cells (SC) following eccentric exercise via activation of estrogen receptor‐α. Insulin‐like Growth Factor‐1 (IGF‐1) is known to cause SC proliferation and differentiation via phosphatidylinositol 3‐kinase (PI3K) signaling. To determine if E2 regulates SC activity via the PI3K pathway, 64, nine‐week old, ovariectomized Sprague‐Dawley rats were divided into eight treatments groups based on: estrogen status (0.25 mg estrogen pellet or sham), exercise status (90 min run @ 17 m/min, −13.5° or unexercised), PI3K signaling inhibition (0.7 mg Wortmannin/kg Body Weight or saline control). Significant increases in total SCs in soleus muscle (immunofluorescent colocalization of nuclei with Pax7) were seen at 72 hr post‐exercise in rats who were E2‐supplemented (t(62) = 1.89, p = 0.063), exercised (t(62) = 5.723, p < 0.001), and whose PI3K pathway was not inhibited (t(62) = 3.460, p = 0.001). PI3K pathway inhibited animals, regardless of estrogen or exercise status showed no significant enhancement of SC number. Preliminary data suggests that an increase in SC population following exercise in estrogen supplemented females may be mediated via PI3K pathway signaling.