Factors Affecting Anti-Estrogen Binding Site Concentration in Rat Liver

Abstract

It is known that synthetic anti-estrogens such as tamoxifen bind to specific high affinity anti-estrogen binding sites (AEBS), which are distinct from estrogen receptors. These binding sites are widely distributed in animal and human tissues, the highest concentrations being found in the liver. The physiological role of these intracellular binding sites, which are located predominantly in the microsomal fraction, is currently unknown, as is the nature and identity of their endogenous ligands. In an attempt to gain information which may provide clues to the possible physiological role of these binding sites, studies were carried out to determine whether the concentration of these binding sites in rat liver was affected by a number of physiological variables. The results of these studies indicated that in the rat (i) liver AEBS increased progressively with age; (ii) liver AEBS concentration tended to be higher among females than males after 100 days of age; (iii) there was no significant variation in liver AEBS level with different phases of the estrous cycle; (iv) liver AEBS level was not significantly affected by castration in both males and females or by estradiol replacement in castrated females; (v) liver AEBS concentration increased significantly with increases in ambient temperature; (vi) there was no clearly detectable alteration in liver AEBS levels with changes in the light:dark cycle; (vii) starvation for 24, 48, and 72 hr increased liver AEBS by approximately 1.5-, 3-, and 2-fold, respectively, while refeeding decreased its level; and (viii) liver AEBS was not affected by increasing dietary fat content from 0.5% to 20% (w/w), but was increased modestly by the addition of cholesterol (2% w/w) to the diet. These observations identify several physiological variables which are associated with changes in liver AEBS concentration and suggest possible avenues for future studies to define the physiological role of these binding sites.

Side Effects of Tamoxifen in Oophorectomized Rats

“…We also did not detect any histological change in the liver of TAM-treated animals compared to OX control and sham-operated rats. TAM was demonstrated to bind to the specific antiestrogenbinding sites in the liver as in various organs in rat, and the concentration of these binding sites was not affected by the steroid hormone changes [37]. Also, TAM was reported to act as a promoter rather than an initiator in the hepatocarcinogenesis by Dragan et al [38].…”