17β-Hydroxysteroid dehydrogenases (17β-HSDs) are oxidoreductases, which play a key role in estrogen and androgen steroid metabolism by catalyzing the final steps of steroid biosynthesis.
Considering the pivotal role of 17β-HSDs in steroid hormone modulation and their substrate specificity, these enzymes are promising therapeutic targets for diseases like breast cancer, endometriosis and prostate cancer.
We are particularly interested in inhibiting 17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) for the treatment of endometriosis. The development of endometriosis is estrogen-dependent. Estradiol, the most active form, is produced either from estrone via 17β-HSD1 or from testosterone via aromatase. Expression levels of 17β-HSD1 and activity of the enzyme are elevated in endometrial tissue of patients suffering from this chronic disease. Moreover, a genetic polymorphism Ser312Gly of 17β-HSD1 is associated with increased levels of E2 as well as endometriotic risk and severity.
The potent and selective 17β-HSD1 inhibitor will be evaluated in an in vivo model of endometriosis. The xenograft model where human endometrial tissue is inoculated in nude mice is considered an extremely important tool to study endometriosis. Measurement of the number and size of endometrial lesions will be examined. The desired end result is the confirmation that we have identified a compound for the treatment of endometriosis.