J. Neurochem. (2012) 121, 157â167.
Abstract
Chronic nicotine and oral contraceptive (NOC) exposure caused significant loss of hippocampal membraneâbound estrogen receptorâbeta (ERâÎČ) in female rats compared with exposure to nicotine alone. Mitochondrial ERâÎČ regulates estrogenâmediated mitochondrial structure and function; therefore, investigating the impact of NOC on mitochondrial ERâÎČ and its function could help delineate the harmful synergism between nicotine and OC. In this study, we tested the hypothesis that NOCâinduced loss of mitochondrial ERâÎČ alters the oxidative phosphorylation system protein levels and mitochondrial respiratory function. This hypothesis was tested in hippocampal mitochondria isolated from female rats exposed to saline, nicotine, OC or NOC for 16âdays. NOC decreased the mitochondrial ERâÎČ protein levels and reduced oxygen consumption and complex IV (CIV) activity by 34% and 26% compared with salineâ or nicotineâadministered groups, respectively. We also observed significantly low protein levels of all mitochondrialâencoded CIV subunits after NOC as compared with the nicotine or saline groups. Similarly, the silencing of ERâÎČ reduced the phosphorylation of cyclicâAMP response element binding protein, and also reduced levels of CIV mitochondrialâencoded subunits after estrogen stimulation. Overall, these results suggest that mitochondrial ERâÎČ loss is responsible for mitochondrial malfunction after NOC.