Finasteride: Difference between revisions

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Cody J Cubbage, Michal Harel, Joel L. Sussman, Alexander Berchansky

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 [[Image: Biochem group project.PNG|thumb|500px|right|'''Fig. 3'''. Proposed mechanism of inhibition by Bull et. al. Image shows how the inhibition of 5alpha-reductase is achieved  as Finasteride is used as a substrate to create an enolate intermediate, similar to the one made  during the reduction of testosterone. However, the complex created does not allow for the proton transfer needed to complete the reduction of NADP-Dihydrofinasteride  to Finasteride, because of the change in the carbanion position. PADPR= phosphoadenosine diphosphoribose<ref name="five">Bull, Herbert G.*Garcia-Calvo,Margarita Andersson,Stefan†, Baginsky, Walter F.,Chan,H. Karen,Ellsworth,‡ Dina E., Miller,§ Randall R., Stearns,Ralph A.,Bakshi,Raman K.,Rasmusson, Gary H.,Tolman,Richard L., Myers,Robert W.,Kozarich,John W.,Harris,Georgianna S. (1995, August 6) Mechanism-Based Inhibition of Human Steroid 5R-Reductase by Finasteride: Enzyme-Catalyzed Formation of NADP-Dihydrofinasteride, a Potent Bisubstrate Analog Inhibitor. </ref>]]
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 ==Medical Uses==
 ==='''Benign Prostatic Hyperplasia (BPH)'''===
-[[Aromatase]] and 5α-reductase is responsible for converting androgen hormones into estrogen and dihydrotestosterone (DHT). This chemical process of androgen hormones leads to a decrease in testosterone, but raises levels of DHT and estrogen <ref name="eight">Tacklind, J., Fink, H.A., MacDonald, R., Rutks, I., Wilt, T.J. (2010).  Finasteride for benign prostatic hyperplasia. Cochrane database of systematic reviews 2010, Issue 10. Art. No.: CD006015. DOI: 10.1002/14651858.CD006015.pub3. </ref>. Estrogen is a key role in cells proliferating in the prostate and DHT is an anabolic hormone much more potent (dissociated from the androgen receptor slowly) than testosterone that when combined, causes a synergy to induce BPH <ref name="nine">Dragan, I., Misso, M. (2012). Lycopene for the prevention and treatment of benign prostatic hyperplasia and prostate cancer: A systematic review. Maturitas, 72 (4), 269 </ref>. The enzyme 5α-reductase is responsible for the synthesis of DHT in the prostate from circulating testosterone. 5α-reductase is located in the stromal cells, which is the main site for the synthesis of DHT, but it can also diffuse into epithelial cells close-by. In both stromal and epithelial cells, DHT binds to nuclear androgen receptors and signals for transcription for cell growth. Finasteride is used to inhibit the 5α-reductase enzyme, which blocks the conversion of testosterone and inhibits the production of DHT, reducing prostate volume and BPH symptoms (urinating complication). Using finasteride could increase the risk for erectile dysfunction, decrease libido, and ejaulation disorder due to 5α-reductase being inhibited.
+[[Aromatase]] and 5α-reductase is responsible for converting androgen hormones into estrogen and dihydrotestosterone (DHT). This chemical process of androgen hormones leads to a decrease in testosterone, but raises levels of DHT and estrogen <ref name="eight">Tacklind, J., Fink, H.A., MacDonald, R., Rutks, I., Wilt, T.J. (2010).  Finasteride for benign prostatic hyperplasia. Cochrane database of systematic reviews 2010, Issue 10. Art. No.: CD006015. DOI: 10.1002/14651858.CD006015.pub3. </ref>. Estrogen is a key role in cells proliferating in the prostate and DHT is an anabolic hormone much more potent (dissociated from the androgen receptor slowly) than testosterone that when combined, causes a synergy to induce BPH <ref name="nine">Dragan, I., Misso, M. (2012). Lycopene for the prevention and treatment of benign prostatic hyperplasia and prostate cancer: A systematic review. Maturitas, 72 (4), 269 </ref>. The enzyme 5α-reductase is responsible for the synthesis of DHT in the prostate from circulating testosterone. 5α-reductase is located in the stromal cells, which is the main site for the synthesis of DHT, but it can also diffuse into epithelial cells close-by <ref name= "ten"> Bartsch, G., Rittmaster, R.S., Klocker, H. (2000). Dihydrotestosterone and the concept of 5alpha-reductase inhibition in human benign prostatic hyperplasia. European Urology. 37 (4): 367–80. doi:10.1159/000020181 </ref>. In both stromal and epithelial cells, DHT binds to nuclear androgen receptors and signals for transcription for cell growth. Finasteride is used to inhibit the 5α-reductase enzyme, which blocks the conversion of testosterone and inhibits the production of DHT, reducing prostate volume and BPH symptoms (urinating complication). Using finasteride could increase the risk for erectile dysfunction, decrease libido, and ejaulation disorder due to 5α-reductase being inhibited <ref name=""> Robaire, B., Henderson, N.A. (2006). Actions of 5alpha-reductase inhibitors on the epididymis. Molecular and Cellular Endocrinology. 250 (1-2): 190–5. doi:10.1016/j.mce.2005.12.044 </ref>.
 ==='''Prostate Cancer'''===
-Prostate cancer is an androgen dependant adenocarcinoma. The FDA has not approved finasteride as a treatment for prostate cancer. A warning was added, 5α-reductase inhibitors concerning an increased risk of high-grade prostate cancer, as the treatment of BPH lowers PSA (prostate-specific antigen), which could mask that prostate cancer is present.
+Prostate cancer is an androgen dependant adenocarcinoma. The FDA has not approved finasteride as a treatment for prostate cancer. A warning was added, 5α-reductase inhibitors concerning an increased risk of high-grade prostate cancer, as the treatment of BPH lowers PSA (prostate-specific antigen), which could mask that prostate cancer is present <ref name=""> Wilt, T.J., MacDonald, R., Hagerty, K., Schellhammer, P., Kramer, B.S. (2008). Five-alpha-reductase Inhibitors for prostate cancer prevention. Cochrane Database Syst Rev (2): CD007091. doi:10.1002/14651858.CD007091. </ref>.
 ==='''Androgenetic Alopecia (AGA)'''===