Inhibitors of 17β-hydroxysteroid dehydrogenase type 3 in the treatment of prostate cancer

INHIBITORS OF 17Β-HYDROXYSTEROID DEHYDROGENASE TYPE 3 IN THE TREATMENT OF PROSTATE CANCER Name Grade Course: Tutor`s Name: (September 30, 2011) Inhibitors of 17β-hydroxysteroid dehydrogenase type 3 in the treatment of prostate cancer Abstract 17 ß-hydroxysteroid dehydrogenase (17ß-HSD) type 3 is an enzyme found in high amounts in the testes and plays a major role in biosynthesis of androgens such as testosterone hormone which is responsible for both internal and physical male characteristics. The role of 17ß-HSD type 3 in Prostate cancer treatment has widely been studied with emphasis on the inhibitors of the enzyme. In normal cells, 17ß-HSD type 3 enzymes have binding sites on androgen receptors on to which they bind and enhance transcription of genes that facilitate their multiplication. In cancer, the activity of 17ß-HSD type 3 has been observed to be much higher as compared to normal cells and gene transcription for the enzyme occurs in 15 minutes or less. Various studies show that inhibitors do exist that compete for the 17ß-HSD type 3 binding sites on the androgen receptors and others that block the enzymes from binding onto the androgen receptors, these have been broadly divided into two groups namely steroidal and non-steroidal inhibitors. By so doing the inhibitors alter the activity of 17ß-HSD type 3 hence reducing the amount of testosterone in blood and in the prostate. Many existing prostate cancer treatment modes including castration aim at lowering the levels of testosterone and following the fact that many inhibitors leading to the same effect exist, prostate cancer treatment can be enhanced through this manner. Introduction 17 ß-hydroxysteroid dehydrogenases (17ß-HSD) are enzymes found in humans and other animals such as rats; they are common in the testes, placenta and ovaries (Penning, 1996). The 17 ßHSD exist as isoenzymes and in general are responsible for the biosynthesis of the male and female sex hormones testosterone and estrogen, they catalyze the last step in the formation of these hormones. The common isoforms of the 17-ßHSD are namely type 1, type 2 , type 3 and type 4 and type 5, although other types up to type 15 exist. The type 3 17ß-HSD have been observed to be largely located in the testes prostate and seminal vesicles (Vicker, Sharland & Heaton et al, 2008). In the testes, the type 3 17ß-HSD plays an important role in synthesis of androgens by converting the 4-di-one substrate into testosterone. Given the significant role of the 17ß-HSD type 3 in biosynthesis of testosterone, there has been an increased interest in this particular type of 17ß-HSD with relation to treatment of prostate cancer because the androgen receptor has been observed to provide room for further growth and spread or prostate tumors (Narizhneva, Tararova & Ryabokon et al, 2009). Various researches show that inhibition of 17ß-HSD type 3 leads to production of low levels of androgens or none at all hence an effective anti-cancer mechanism. This paper will discuss of the inhibitors of 17ß-HSD type 3 especially in treatment of prostate cancer. Discussion 17ß-HSD type 3 is so crucial for the normal development of ...