These data suggest that the increase in SC population following exercise in oestrogen-supplemented females may be mediated via PI3K pathway signalling and not IGF-1.

https://mc06.manuscriptcentral.com/cjpp-pubs Aim: This study examined the effects of a delay in post-ovariectomy replacement of 17β-estradiol (estrogen) on the post-exercise proliferation of muscle satellite cells.Methods: Nine-week old, ovariectomized female Sprague-Dawley rats (n=64) were divided into eight groups based on: estrogen status (0.25 mg estrogen pellet or sham), exercise status (90 min run @ 17 m/min, -13.5° or unexercised) and estrogen replacement ("proximal"; estrogen replacement within twoweeks or "delayed"; estrogen replacement at eleven-weeks following ovariectomy).Results: Significant increases in satellite cells were found in the soleus and white gastrocnemius muscle (immunofluorescent co-localization of nuclei with Pax7) 72 hrs following eccentric exercise (p < 0.05) in all exercised groups. "Proximal" E2 replacement resulted in a further augmentation of muscle satellite cells in exercised rats (p < 0.05) relative to the delayed estrogen replacement group. Expression of PI3Kwas unaltered and phosphorylation of Akt relative to total Akt increased following estrogen supplementation and exercise. Exercise alone did not alter the expression levels of Akt.Conclusion: An 11 week delay in post-ovariectomy estrogen replacement negated the augmenting influence seen with "proximal" (2 week delay) post-ovariectomy estrogen replacement on post-exercise muscle satellite cell proliferation. This effect appears to be independent of the PI3K/Akt signaling pathway.

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.

17β‐Estradiol (E2) enhances activation, proliferation and differentiation of muscle satellite cells (SCs) following exercise via activation of estrogen receptor‐α (ER) and phosphatidylinositol 3‐kinase (PI3K) signaling. Supplementation of E2 through hormone replacement has been shown to ameliorate muscle atrophic effects of menopause in women. Delay in post‐menopause E2 replacement in humans or following ovariectomy in rodents has resulted in negation of positive health or regenerative effects of E2 on various tissues. To determine if delay in E2 replacement influenced E2 effects on skeletal muscle, 64, nine‐week old, ovariectomized Sprague‐Dawley rats were divided into eight groups based on: E2 status (0.25 mg estrogen pellet or sham), exercise status (90 min run @ 17 m/min, ‐13.5° or unexercised) and E2 replacement (“proximal”; E2 replacement within one week or “delayed”; eleven‐weeks following ovariectomy). Significant increases in total SCs were found in soleus muscle (immunofluorescent co‐localization of nuclei with Pax7) 72 hr following eccentric exercise (p < 0.05). Only “proximal” estrogen‐replacement resulted in further enhancement in total muscle SCs in exercised rats (p < 0.05). Delayed estrogen‐supplementation did not produce a further augmentation in post‐exercise SCs. This suggests the existence of a short window of opportunity where E2 replacement must commence following loss of endogenous estrogen production in order for benefits to skeletal muscle regeneration to manifest. Grant Funding Source: Supported by NSERC