Proposed hypothesized diagram.

Our hypothesis proposed that ovariectomy attenuated the estrogen receptor related survival pathway (ERα, ERβ, IGF-1, IGF-1R, p-PI3K, p-Akt, Bcl-2, Bcl-xL and p-Bad) and activated the cardiac mitochondria-dependent apoptotic pathway (t-Bid, Bad, Bax, Cytochrome c, activated caspase-9, and activated caspase-3), as well as activated the cardiac Fas receptor-dependent apoptotic pathway (TNF-α, Fas ligand, Fas receptors, activated caspase-8, and activated caspase-3) after an ovariectomy. However, the estrogen receptor enhanced the related survival pathway and suppressed the cardiac Fas receptor-dependent as well as the mitochondria-dependent apoptotic pathway which were observed in either the 17β-estradiol (E2) treatment or E2 treatment combined with exercise intervention. Furthermore, the protein levels of ERβ, IGF-1, IGF-1R, Bcl-2 and Bcl-xL were further enhanced when combined with E2 and exercise training. The protein levels of t-Bid, Cytochrome c, Fas receptors, FADD, activated caspase-8, activated caspase-9 and activated caspase-3 were further decreased when combined with E2 and exercise training.