Steroid Sulfatase and Sulfotransferase By Ronald Steriti, ND, PhD © 2011

Steroid sulfatase (or steryl-sulfatase), formerly known as Arylsulfatase C, is a sulfatase enzyme involved in the metabolism of . It is encoded by the STS gene. Metabolism Steroid sulfatase catalyzes the hydrolysis of sulfated steroids, such as and dehydroepiandrosterone sulfate (DHEAS), to non- sulfated steroids estradiol and , respectively. (Reed, Purohit et al. 2005)

Deficiency A deficiency is associated with X-linked ichthyosis, a scaly-skin disease affecting roughly 1 in every 2,000-6,000 males. (Ghosh 2004) Excess Increases in serum level are associated with increased mammographic density during menopausal hormone therapy. (Crandall, Guan et al. 2008) Estrone sulfate (E1S) may be a prognosis marker for tumor aggressiveness in . (Giton, de la Taille et al. 2008) Conventional Treatments

Irosustat Irosustat is a first-generation steroid sulfatase inhibitor used in cancer. (Palmieri, Januszewski et al. 2011) Hormone Therapies

Melatonin Melatonin, at physiologic concentrations, modulates the synthesis and transformation of biologically active in MCF-7 cells, through the inhibition of sulfatase (STS) and 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) activity and expression, enzymes involved in the estradiol formation in cells. (Gonzalez, Alvarez-Garcia et al. 2010) (Gonzalez, Martinez-Campa et al. 2010)

Progesterone Estrogen is degraded by estrogen sulfotransferase (EST) (a selenium enzyme), which is regulated by the levels of progesterone. Natural Therapies

Boronic acids Boronic acids inhibit steroid sulfatase. (Ahmed, Liu et al. 2006)

Black Cohosh Extracts of black cohosh (Actaea racemosa) inhibits the conversion of estrone sulphate to active estradiol. (Rice, Amon et al. 2007)

Phytoestrogens Phytoestrogens are potent inhibitors of estrogen sulfation. (Harris, Wood et al. 2004)

Quercetin Quercetin is a potent inhibitor of estrone sulfatase in vitro. (Huang, Fasco et al. 1997)

Alcohol Moderate alcohol consumption (15 g/d, 30 g/d) for 8 weeks resulted in significantly increased levels of serum estrone sulfate and DHEAS in 51 postmenopausal women in a randomized, placebo-controlled trial. (Mahabir, Baer et al. 2004) Summary Steroid sulfatase (SST) inhibitors include: Irosustat, melatonin, Boronic acids, and Phytoestrogens. Estrogen sulfotransferase (EST) is a selenium enzyme that is regulated by the levels of progesterone. Inhibitors include: Black cohosh, and Quercetin.

References

Ahmed, V., Y. Liu, et al. (2006). "Boronic acids as inhibitors of steroid sulfatase." Bioorg Med Chem 14(24): 8564-73. Crandall, C. J., M. Guan, et al. (2008). "Increases in serum estrone sulfate level are associated with increased mammographic density during menopausal hormone therapy." Cancer Epidemiol Biomarkers Prev 17(7): 1674-81. Ghosh, D. (2004). "Mutations in X-linked ichthyosis disrupt the active site structure of estrone/DHEA sulfatase." Biochim Biophys Acta 1739(1): 1-4. Giton, F., A. de la Taille, et al. (2008). "Estrone sulfate (E1S), a prognosis marker for tumor aggressiveness in prostate cancer (PCa)." J Steroid Biochem Mol Biol 109(1-2): 158-67. Gonzalez, A., V. Alvarez-Garcia, et al. (2010). "In vivo inhibition of the estrogen sulfatase enzyme and growth of DMBA-induced mammary tumors by melatonin." Curr Cancer Drug Targets 10(3): 279-86. Gonzalez, A., C. Martinez-Campa, et al. (2010). "Inhibitory effects of melatonin on sulfatase and 17beta-hydroxysteroid dehydrogenase activity and expression in glioma cells." Oncol Rep 23(4): 1173-8. Harris, R. M., D. M. Wood, et al. (2004). "Phytoestrogens are potent inhibitors of estrogen sulfation: implications for breast cancer risk and treatment." J Clin Endocrinol Metab 89(4): 1779-87. Huang, Z., M. J. Fasco, et al. (1997). "Inhibition of estrone sulfatase in human liver microsomes by quercetin and other flavonoids." J Steroid Biochem Mol Biol 63(1-3): 9-15. Mahabir, S., D. J. Baer, et al. (2004). "The effects of moderate alcohol supplementation on estrone sulfate and DHEAS in postmenopausal women in a controlled feeding study." Nutr J 3: 11. Palmieri, C., A. Januszewski, et al. (2011). "Irosustat: a first-generation steroid sulfatase inhibitor in breast cancer." Expert Rev Anticancer Ther 11(2): 179-83. Reed, M. J., A. Purohit, et al. (2005). "Steroid sulfatase: molecular biology, regulation, and inhibition." Endocr Rev 26(2): 171-202. Rice, S., A. Amon, et al. (2007). "Ethanolic extracts of black cohosh (Actaea racemosa) inhibit growth and oestradiol synthesis from oestrone sulphate in breast cancer cells." Maturitas 56(4): 359-67.