Bombardier E, Vigna C, Iqbal S, Tiidus PM, Tupling AR. Effects of ovarian sex hormones and downhill running on fiber-type-specific HSP70 expression in rat soleus. J Appl Physiol 106: 2009 -2015, 2009. First published April 9, 2009 doi:10.1152/japplphysiol.91573.2008This study examined the influence of the ovarian sex hormones, estrogen and progesterone, on the fiber-type-specific response of the inducible 70-kDa heat shock protein (HSP70) to damaging exercise in rat soleus. Ovariectomized female rats were divided into three treatment groups (n ϭ 16 per group): sham (S), progesterone (P; 25 mg pellet), and estrogen (E; 0.25 mg pellet). Each treatment group was divided into control and exercised groups. After 8 days of sham or hormone treatment, animals ran downhill intermittently for 90 min (17 m/min, Ϫ13.5°grade) on a treadmill, and soleus muscles were removed 24 h postexercise. HSP70 expression was assessed in whole muscle homogenates by Western blotting and in individual muscle fiber types by immunohistochemical analysis of serial cross sections of soleus samples. Comparisons between control groups showed that HSP70 expression in soleus was increased (P Ͻ 0.05) in E compared with both S and P. No difference (P Ͼ 0.05) was observed between S and P. Following downhill running, HSP70 content in soleus was increased (P Ͻ 0.05) compared with control in S and P, but not (P Ͼ 0.05) in E. As a result, soleus HSP70 content following downhill running was not different (P Ͼ 0.05) between any of the treatment groups. Under all conditions, HSP70 content was higher in type I vs. type II fibers, and the effects of both estrogen and exercise on HSP70 expression in soleus were also more pronounced in type I vs. type II fibers. These results demonstrate that 1) estrogen regulates HSP70 expression in skeletal muscle, increasing basal HSP70 expression and preventing further increases in HSP70 in response to exercise; 2) progesterone is not involved in the regulation of HSP70 expression in skeletal muscle; and 3) the effects of estrogen and exercise on HSP70 expression in skeletal muscle are fiber type specific. estrogen; progesterone; muscle fiber type HEAT SHOCK PROTEINS (HSP) are families of highly conserved stress proteins found in almost all cells, which have been shown to be induced by a variety of environmental and intracellular stresses (18). The inducible 70-kDa HSP (HSP70) may be the most highly induced protein of the cellular stress response and is rapidly upregulated under conditions of oxidative stress (48). It is well established that HSP70 content in skeletal muscle increases in response to both nondamaging and damaging exercise and can protect against contraction-induced muscle damage (for review, see Refs. 10,19). However, the HSP70 response to exercise in both skeletal (31, 33) and cardiac muscle (32) is sex specific, with males demonstrating a more robust response than females. Collectively, these studies and others have shown that the sex-specific HSP70 response to exercise is mediated by the ovarian sex hormo...