β-estradiol effect on erythrocyte aggregation : a controlled in vitro study

Abstract

17β-estradiol as free radical scavengers is a steroid hormone, unionised and lipophilic at physiological pH. Fifteen to 35% of the total amount of steroids in the blood is transported by red blood cells that carry 17β-estradiol, both membrane-bound (two thirds) and in the cytoplasma (one third of the 17β-estradiol) being the erythrocytes responsible for 5–15% of sex hormone delivery to target tissues [1,2]. Its importance has been lately pointed out for its cardiovascular risk reduction in postmenopausal women [3] although the mechanism of this cardioprotective effect remain unclear. An antioxidant role as free radical scavengers has been demonstrated which could explain the protective role [4,5]. The work of Mc Manus et al. [6] did not support the role of oestrogens as antioxidants in vivo, besides the lower plasma hydroperoxide level determined four weeks after insertion of the estradiol implant. Previously data in primate have been shown that chronic 17β-estradiol supplementation decreased LDL accumulation in vivo [7]. Several studies on estrogen effects on the blood vessel wall are arising [8,9] and it was suggested previously an increasing production of nitric oxide induced by estrogen, that may contribute to the improvement in myocardial metabolic disfunction by increasing coronary blood flow [10]. An increase in blood flow in the peripheral arteries was verified after administration of hormone replacement therapy in women who had undergone surgical menopause [11]. So in what concerns the hemorreologic properties Coata et al. showed that low-dose triphasic contraceptives does not seem to affect blood viscosity [12] and in another study it was verified that the estrogen replacement therapy lowering plasma viscosity in a group of 23 women [13]. The effect of 17β-estradiol on membranes has been the aim of some studies focusing epithelial cell membranes that seemed to become more fluid [14]. Other studies, on microvilli, indicate that estradiol acts on the lipid composition of membranes, probably changing the phospholipids availability [15]. Moreover the membrane action of sex steroids on other elements of the erythroid line (reticulocytes) has been reported to be of different extent than the traditional nuclear action of steroids [16]. Jacobson et al. mentioned that steroid binding to membrane proteins is associated with short term cytophysiological events such as ion fluxes. However, they believe long-term genomic responses involving intracellular receptors follows another route determined by membrane lipid [17], which shows the relevance of the membrane properties and subsequently the hemorheological importance of estradiol in blood. Recently Levin’s group also showed that estrogen, via a signal transduction pathway governed by membrane receptors, could both rescue endothelial cells from a hypoxia induced death and promote new blood vessel formation [18]. As mentioned above the β-estradiol is transported in blood by erythrocyte in a membrane bound way so, it seems possible the occurrence of some erythrocyte functions and properties modifications in presence of estradiol. Therefore the aim of this study was to determine the 17β-estradiol effect on the hemorheological and biochemical properties of postmenopausal women erythrocytes.