Tibolone: a compound with tissue specific inhibitory effects on sulfatase

The aim was to test whether sulfatase activity is differently regulated by tibolone in human bone, endometrium and breast cells since selective inhibi tion of sulfatases in various tissues may contribute to the tissue-specific ity of tibolone. Tibolone, its 3 alpha- and 30-hydroxy metabolites and thei r 3-sulfated forms, and its Delta (4)-isomer strongly (70-90%) inhibited th e sulfatase activity in human breast cell lines (two T-47D clones) and inte rmediately (8-43%) in human endometrial cells (HEC-1A). In contrast, they d id not inhibit sulfatase in two human osteoblast-like cell lines (MG 63, HO S TE-85), The specific sulfatase inhibitor, EMATE, showed inhibition in all cell lines. Just as estrone sulfate, 3 alpha -sulfated tibolone was also c onverted by sulfatase to the unconjugated 3 alpha -hydroxy-tibolone intrace llularly in all cell lines. The tissue specific inhibition pattern of sulfa tase activity by tibolone and its metabolites suggest that tibolone could b e protective against development of mammary carcinomas, whereas it retains favorable estrogenic effects on bone. (C) 2001 Elsevier Science Ireland Ltd . All rights reserved.