In SULT1E1 knock-out mice, loss of SULT1E1 causing an excess of estrogens leads to the formation of smaller patches from white fat and insulin resistance [97]. In type 2 diabetes, induction of hepatic SULT1E1 is most

frequently observed. Loss of SULT1E1 improves the metabolic function in a female mouse model of type 2 diabetes, restores insulin sensitivity, and blocks hepatic gluconeogenesis and lipogenesis [98]. Since in diabetes, upregulation of SULT1E1 decreases E2 levels, inactivation of the enzyme will prevent loss of estrogens and normalize estrogenic activity in the liver. Inhibitors,research,lifescience,medical This beneficial effects of SULT1E1 inactivation were absent in ovariectomized mice. These effects were also sex specific, as SULT1E1 loss in males worsened the diabetic phenotype and led to a decreased islet beta-cell mass, failure Inhibitors,research,lifescience,medical of glucose-stimulated insulin secretion, increased macrophage infiltration, and inflammation in white adipose tissue. The authors suggest that inhibition of SULT1E1 at least in females may represent a novel approach in the therapy of type 2 diabetes [98, 99]. However, it has to be considered that type 2 diabetes mostly occurs in women after the menopause when local formation of steroid hormones from adrenal precursors becomes important. Since extragonadal Inhibitors,research,lifescience,medical estrogen production is typical for primates [2], the benefit of increasing levels of active estrogens

by reducing SULT1E1 may have to be studied in a proper model for type 2 diabetes in this group. In any case, higher estrogen levels are thought to have beneficial effects on type 2 diabetes, but the risk of the induction of hormone-sensitive cancers may be considered as well. 5. Steroid Sulfatase Inhibitors as Agents for a Therapy of Hormone-Sensitive Tumors Inhibitors,research,lifescience,medical Hormone therapy is used to treat both early and advanced breast Inhibitors,research,lifescience,medical cancer and to prevent breast cancer in women who are at high-risk of developing the

disease. Lonafarnib order Currently, the most widely used therapies for the treatment of hormone-dependent cancer is to block the action of steroid hormones. Adjuvant endocrine therapy with the selective estrogen receptor modulator (SERM) tamoxifen is recommended for premenopausal women with a history of atypical hyperplasia to reduce breast cancer risk. Raloxifene, another selective PAK6 estrogen receptor modulator, was found to be equivalent to tamoxifen in reducing the risk of developing invasive breast cancer in postmenopausal women. However, it did not provide the same level of risk reduction for developing noninvasive breast cancer. Aromatase inhibitors, which block the conversion of androstenedione to estrone, are applied in postmenopausal women. Currently, third-generation aromatase inhibitors, which comprise the nonsteroidal compounds anastrozole and letrozole, and the steroidal exemestane are finding widespread application in the clinic (for reviews see [100, 101]).