ER alpha distribution in the female myocardium: impact of senescence and estradiol levels

Background: Ischemia and reperfusion (I/R) injury is increased following menopause and may be associated with disturbances in cardiac estrogen receptor α (ERα) signaling. The role of estrogen receptors (ER) in the heart, particularly with aging, is poorly understood. Purpose: To determine the singular and combined effects of aging and estradiol on cellular distribution of ERα in the female rat heart following I/R. Methods: Adult (Y) and aged (O) female F344 rats (n = 12/age) with ovaries intact or removed (OVX) were subjected to I/R using Langendorff perfusion (31 min global I). Changes in cytosolic (Cyto), nuclear (Nuc), mitochondrial (Mito), and particulate (Part) ERα levels were assessed with Western Blotting. Results: Cyto ERα protein levels decreased with I/R in both Y and O compared to baseline. Reductions in Part and Nuc ERα with I/R also occurred in O and Y+OVX, without further reductions in O+OVX. Mito ERα was reduced in O at baseline and I/R, and reversed by OVX suggesting aberrant ER partitioning (p<0.05). Summary: These data suggest, for the first time, that changes in ERα cellular distribution occur with I/R in the aged female heart which are independent of circulating estradiol levels.