Biocides, tributyltin and triphenyltin, as possible inhibitors of the human sulfotransferase involved in the estrogen homeostasis

This work using purified recombinant human estrogen sulfotransferase (hSULT1E1) aimed to investigate the mechanism of the inhibition of estrogen sulfation by organotin compounds. Tributyltin (TBT) inhibited the sulfation of estrone (E1) and 17 β-estradiol (E2) by hSULT1E1 competitively, with IC50 values of, respectively, 3 and 12 μM. The sulfation of E1 and E2 was also inhibited competitively by triphenyltin (TPT), with IC50 of, respectively, 10 and 5 μM. These data strongly suggested that His107 residue might act as a ligand to establish a coordination bond with organotins at estrogen binding site in hSULT1E1. A more surprising finding was that TBT competed with 3′-phosphoadenosine 5′-phosphosulfate (PAPS), indicating that TBT may coordinate with certain amino acid residue such as Lys47 at the PAPS binding site of hSULT1E1. Taken together, these data provided clear evidence that TBT and TPT have a capacity to disrupt endocrine-mediated events by inhibiting hSULT1E1 involved in the metabolism of sex steroids.