High metabolization of catecholestrogens by type 1 estrogen sulfotransferase (hEST1)

Recently, two types of estrogen sulfotransferase, chronologically named typ es 1 and 2 estrogen sulfotransferase (hEST1 and hEST2), have been described . Since hEST2 selectively catalyzes the sulfonation of ethinyl estradiol as well as that of estrone (E1) and estradiol (E2), but poorly the sulfonatio n of catecholestrogens, we wanted to assess the ability of hEST1 to metabol ize these compounds. We overexpressed hEST1 in Escherichia roll in fusion w ith GST, then purified the enzyme using a glutathione affinity column, and obtained GST-free enzyme by digestion with thrombin. Using [S-35]-phosphosa denosine phosphosulfate (PAPS) as cofactor, we showed that hEST1 efficientl y metabolizes the transformation of 2-OH-E2 and 2-OH-E1. However, the trans formation of 4-OH-E1 and 4-OH-E2 is much less efficient. Our results also s how that hEST1 metabolizes more efficiently E2 than E1. Since hEST1 mRNA is produced from the same gene as MPST using different alternative promoters acid since it is expressed in most breast cancer cells (MCF-7, ZR-75-1, T47 -D, MDA-231, and MDA-418). studies of the expression and activity of hEST1 will be most important to have a better knowledge about its involvement in the control of the genotoxicity of estrogens and catecholestrogens. (C) 200 1 Elsevier Science Ltd. All rights reserved.