75 Original Paper Cell Physiol Biochem 2009;23:75-86 Accepted: November 20, 2008 Cellular Physiology Cellular Physiology Cellular Physiology Cellular Physiology Cellular Physiology and Biochemistr and Biochemistr and Biochemistr and Biochemistr and Biochemistry Copyright © 2009 S. Karger AG, Basel Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com © 2009 S. Karger AG, Basel 1015-8987/09/0233-0075$26.00/0 Accessible online at: www.karger.com/cpb Expression, Distribution and Regulation of Sex Steroid Hormone Receptors in Mouse Heart Eric Lizotte 1,2 , Scott A. Grandy 1,2 , Annie Tremblay 1,2 , Bruce G. Allen 1,3 and Céline Fiset 1,2 1 Research Center, Montreal Heart Institute, 2 Faculty of Pharmacy, Université de Montréal, 3 Department of Medicine, Université de Montréal, Montréal, Quebec Dr. Céline Fiset Research Center, Montreal Heart Institute 5000 Belanger Street, Montreal, Quebec, H1T 1C8 (Canada) Tel. +1 514-376-3330 (Ext. 3025); Fax +1 514-376-1355 E-Mail celine.fiset@umontreal.ca Key Words Cardiac  Ovariectomy  Subcellular distribution  Pro- tein fraction Abstract The effects of sex hormones on the heart are de- pendent on the presence and distribution of sex ster- oid hormone receptors (SSHR) in cardiac tissue. This study used subcellular fractionation, Western blot analysis and densitometry to characterize the sub- cellular distribution and abundance of estrogen receptor (ER) α, ERβ and androgen receptor (AR) in atrial and ventricular tissue from male and female mice. The results showed that in both atrial and ven- tricular tissue ERα was primarily found in the sarco- lemma, whereas ERβ and AR were predominantly lo- cated in the nucleus and cytosol. Interestingly, ERα expression was greater in the ventricles compared to the atria, whereas ERβ and AR expression were simi- lar in both heart chambers. Furthermore, the distri- bution and abundance of SSHR in the atria and ven- tricles did not differ between sexes. This study also showed that a reduction in hormone levels (as a re- sult of ovariectomy) resulted in a significant increase in the abundance of ERα in the ventricular sarco- lemmal fraction. Overall, the results suggest ERα, ERβ and AR distribution and expression are not sex dependent in the mouse heart. However, it appears that ERα expression is chamber specific and that, in certain cases, hormone levels can modulate the sub- cellular location of SSHRs. Introduction Cardiovascular diseases are the leading cause of mortality for both men and women throughout most of the industrialized world [1-7]. Interestingly, women tend to develop heart disease later in life than men [8, 9]. In fact, the incidence of cardiovascular diseases only begins to steadily increase in women after the onset of menopause [10]. It is believed that the late onset of cardiovascular disease in women is partially attributable to sex differences in sex steroid hormones [8]. Specifically, endogenous estrogen may have a cardioprotective effect in premenopausal women [9]. Furthermore, evidence suggests that the male sex hormones may play a role in the development of certain types of cardiovascular disease [11, 12]. Thus it appears