The Sulfatase Pathway for Estrogen Formation: Targets for the Treatment and Diagnosis of Hormone-Associated Tumors

Figure 1

Estrone sulfate (E1S), androstenediol-sulfate (Adione-S), and dehydroepiandrosterone-sulfate (DHEA-S) are taken up into cells by organic anion transporting polypeptides (OATPs) and other transporters from the SLC-family. The “sulfatase pathway,” estrone-3-sulfate (E1S), is taken up by the cells and is activated by the removal of sulfate by the steroid sulfatase (STS). E1 is converted to the biological most active estrogen, 17beta-estradiol (E2), by reductive 17beta-hydroxysteroid dehydrogenases (17beta-HSDs). E2 binds and activates estrogen receptors. Vice versa, the conversion of E2 to less active E1 is catalysed by oxidative 17beta-HSDs. For inactivation, E1 is sulfonated by estrogen sulfotransferase SULT1E1 to E1S. The “aromatase pathway,” 5alpha-androstenediol-sulfat (Diol-S) and dehydroepiandrosterone (DHEA), are mainly derived from the circulation. Diol-S is converted 5alpha-androstenediol (5-Diol) by STS. It is converted into testosterone by 3beta-HSD. DHEA-S is hydrolyzed to form DHEA, which is further converted by 3beta-hydroxysteroid dehydrogenase to form androstenedione (4-Dione). Testosterone is formed by 17beta-HSD from 4-Dione. Testosterone is converted to E2 by the aromatase (CYP19). 5-Diol binds and activates estrogen receptors, but with lower affinity than E2 (see [20, 22]).