ESTROGEN SULFOTRANSFERASE EXPRESSION IN THE HUMAN LIVER - MARKED INTERINDIVIDUAL VARIATION AND LACK OF GENDER SPECIFICITY

Estrogen sulfotransferase (EST) catalyzes the specific sulfonation of estrogen at the 3'-hydroxyl position using 3'-phosphoadenosine-5'-phos phosulfate as an activated sulfate donor. Sulfonation renders the horm one biologically inactive as well as changing its half-life within the human body. Studies in the rat and mouse have suggested that expressi on of EST in the liver is age-and sex-dependent, being prominent only in sexually mature young males. Although a human EST cDNA has previous ly been cloned, the characteristics of hepatic EST expression in human subjects remain to be defined. In this study, we have investigated an d 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 exp ression of EST. However, EST protein level in the human liver is corre lated neither with gender nor with age. Interestingly, paired-group an alysis revealed a statistically significant difference in the hepatic expression of EST protein and activity between alcohol users and nonus ers. We conclude that, unlike what is observed in the rodent liver, ES T expression in the human liver is not sex-limited. Thus hepatic EST m ay play a role in estrogen metabolism and homeostasis in both genders of human subjects. The marked individual variation suggests that EST g ene expression is subject to sensitive control by genetic or environme ntal factors. The potential correlation between alcohol consumption an d hepatic EST expression deserves further evaluation.