Identification of a 17p-Hydroxysteroid Dehydrogenase Type 10 Steroidal Inhibitor: A Tool to Investigate the Role of Type 10 in Alzheimer's Disease and Prostate Cancer

摘要

Human 17β-hydroxysteroid dehydrogenase type 10 (17β-HSD10) is known for its multiple functions and could be involved in the development and progression of many diseases.~([1-6]) 17β-HSD10 is a homotetrameric mitochondrial protein expressed in the liver and several other tissues, including brain and gonad. It plays a role in the metabolism of steroid hormones through its 17β-HSD and 3a-HSD activities (Scheme 1),and can also generate dihydrotestosterone (DHT), the most potent steroid responsible for androgenic activity in men. Furthermore, 17β-HSD10 is the only hydroxysteroid dehydrogenase known to have a moderate affinity for amyloid β-peptide (Aβ),~([5]) the accumulation of which is a characteristic of Alzheimer's disease (AD).~([7,8]) The properties of 17β-HSD10 are interesting and suggest a possible role in two important diseases, AD and prostate cancer (PC).