Estrogen Sulfotransferase Expression in the Human Liver: Marked Interindividual Variation and Lack of Gender Specificity

Abstract

Estrogen sulfotransferase (EST) catalyzes the specific sulfonation of estrogen at the 3′-hydroxyl position using 3′-phosphoadenosine-5′-phosphosulfate as an activated sulfate donor. Sulfonation renders the hormone biologically inactive as well as changing its half-life within the human body. Studies in the rat and mouse have suggested that expression of EST in the liver is age- and sex-dependent, being prominent only in sexually mature young males. Although a human EST cDNA has previously been cloned, the characteristics of hepatic EST expression in human subjects remain to be defined. In this study, we have investigated and compared the expression of EST in 10 human liver samples by using an EST-specific antibody and performing enzyme activity assays. We found a marked interindividual variation (up to 25-fold) in the hepatic expression of EST. However, EST protein level in the human liver is correlated neither with gender nor with age. Interestingly, paired-group analysis revealed a statistically significant difference in the hepatic expression of EST protein and activity between alcohol users and nonusers. We conclude that, unlike what is observed in the rodent liver, EST expression in the human liver is not sex-limited. Thus hepatic EST may play a role in estrogen metabolism and homeostasis in both genders of human subjects. The marked individual variation suggests that EST gene expression is subject to sensitive control by genetic or environmental factors. The potential correlation between alcohol consumption and hepatic EST expression deserves further evaluation.