Estrogen Attenuates Post-Exercise Hsp70 Expression in Skeletal Muscle Running Title: Sex-specific Hsp70 induction

Exercise has been demonstrated as a physiological inducer of Hsp70. Many of the factors associated with exercise proposed to signal this response demonstrate sexual dimorphism. Thus, the present objectives were to determine if Hsp70 induction following exercise exhibited gender-specificity and to elucidate the mechanisms underlying such a phenomenon. Post-exercise Hsp70 induction in skeletal muscle was greater in male rats than females at the level of protein and mRNA (p = 0.005). Moreover, placebo treated ovariectomized animals demonstrated a greater Hsp70 response to exercise than those estrogen-treated (p = 0.015 and 0.019 for protein and mRNA, respectively). These findings indicate that the gender-specific Hsp70 response to exercise is mediated by the female-specific hormone estrogen. Compounds structurally related to 17β-estradiol, the major endogenous estrogen, but which do not activate the estrogen receptor, also attenuated Hsp70 induction with exercise (p < 0.01), indicating a non-genomic hormonal mechanism. These findings highlight a specific example of the biological differences between males and females and reiterate the physiological effects of sex hormones extending beyond their roles in reproductive function.