Introduction: Benign and malignant prostate diseases are among the most common in elderly men. Androgens, mainly testosterone and dihydrotestosterone (DHT), play an important role to maintain normal prostate growth and proliferation. It is considered that an imbalance between androgen-induced cell proliferation and apoptosis is one of the major factors for increased cell proliferation, growth and development of neoplastic prostate gland diseases.
The aim of our study is to perform a literature search regarding the specifics of androgen metabolism in normal and cancerous prostate gland.
Material and Methods: Scientific literature from the last 10 years has been studied using the online databases of Scopus, PubMed, Google Scholar, and Science direct. The following key words and phrases were used: prostate cancer, benign prostate hyperplasia, androgens, testosterone, DHEAs, androstenedione, SHBG, androgen metabolism.
Results: Some of the most common changes in androgen metabolism regarding prostate diseases are the increased intracrine prostate androgen biosynthesis, the reduced local inactivation and polymorphisms of the androgen receptor.
Conclusion: Clarification of the molecular mechanisms controlling the androgen metabolism in prostate cells and their changes in prostate gland diseases would contribute to elucidate the role of these steroid hormones for the onset and progression of benign and malignant prostate diseases.
Albuquerque G, Guglielmetti G, Barbosa J, Pontes J, Fazoli A, Cordeiro M, Coelho R, Carvalho P, Gallucci F, Padovani G, Park R, Cury J, Nonemacher H, Srougi M, Nahas W. Low serum testosterone is a predictor of high-grade disease in patients with prostate cancer. Rev Assoc Med Bras (1992). 2017;63(8):704-710.
Barbier O, Bélanger A. Inactivation of androgens by UDP-glucuronosyltransferases in the human prostate. Best Pract Res Clin Endocrinol Metab. 2008;22(2):259-70.
Bayar G, Şirin H, Aydın M, Özağarı A, Tanrıverdi O, Kadıhasanoğlu M, Kendirci M. Low free and bioavailable testosterone levels may predict pathologically-proven high-risk prostate cancer: a prospective, clinical trial. Turk J Urol. 2017;43(3):289-296.
Capper C, Rae J, Auchus R. The Metabolism, Analysis, and Targeting of Steroid Hormones in Breast and Prostate Cancer. Horm Cancer. 2016;7(3):149-64.
Chang K, Li R, Papari-Zareei M, Watumull L, Zhao Y, Auchus R, Sharifi N. Dihydrotestosterone synthesis bypasses testosterone to drive castration-resistant prostate cancer. Proc Natl Acad Sci U S A. 2011;108(33):13728-33.
Chang K, Ercole C, Sharif N. Androgen metabolism in prostate cancer: from molecular mechanisms to clinical consequences. Br J Cancer. 2014;111(7):1249-1254.
Elahe A. Steroid hormone synthetic pathways in prostate cancer. Transl Androl Urol. 2013;2(3):212-227.
Fujimura T, Takahashi S, Urano T, Kumagai J, Murata T, Takayama K, Ogushi T, Horie-Inoue K, Ouchi Y, Kitamura T, Muramatsu M, Homma Y, Inoue S. Expression of Cytochrome P450 3A4 and Its Clinical Significance in Human Prostate Cancer. Urology 2009;74(2):391-397.
Gann P, Hennekens C, Ma J, Longcope C, Stampfer M. Prospective study of sex hormone levels and risk of prostate cancer. J Natl Cancer Inst. 1996;88(16):1118-26.
Gauthier-Landry L, Bélanger A, Barbier O. Multiple roles for UDP-glucuronosyltransferase (UGT)2B15 and UGT2B17 enzymes in androgen metabolism and prostate cancer evolution. J Steroid Biochem Mol Biol. 2015;145:187-92.
Guillemette C, Lévesque E, Beaulieu M, Turgeon D, Hum D, Bélanger A. Differential regulation of two uridine diphospho-glucuronosyltransferases, UGT2b15 and UGT2b17, in human prostate LNCaP cells. Endocrinology. 1997;138(7):2998-3005.
Huggins C, Hodges C. Studies on prostatic cancer. I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. CA Cancer J Clin. 1972;22(4):232-40.
Klap J, Schmid M, Loughlin K. The relationship between total testosterone levels and prostate cancer: a review of the continuing controversy. J Urol. 2015;193(2):403-13.
Locke J, Guns E, Lubik A, et al. Androgen levels increase by intratumoral de novo steroidogenesis during progression of castration-resistant prostate cancer. Cancer Res. 2008;68:6407-6415.
Luu-The V, Bélanger A, Labrie F. Androgen biosynthetic pathways in the human prostate. Best Pract Res Clin Endocrinol Metab. 2008;22(2):207-21.
Mohler J, Titus M, Bai S, Kennerley B, Lih F, Tomer K, Wilson E. Activation of the androgen receptor by intratumoral bioconversion of androstanediol to dihydrotestosterone in prostate cancer. Cancer Res. 2011;71(4):1486-96.
Morgentaler A, Rhoden E. Prevalence of prostate cancer among hypogonadal men with prostate-specific antigen levels of 4.0 ng/mL or less. Urology. 2006;68(6):1263-7.
Morgentaler A. Goodbye androgen hypothesis, hello saturation model. Eur Urol. 2012;62(5):765-7.
Morgentaler A, Conners P. Testosterone therapy in men with prostate cancer: literature review, clinical experience, and recommendations. Asian J Androl. 2015;17(2):206-211.
Penning T. Androgen biosynthesis in castration-resistant prostate cancer. Endocr Relat Cancer. 2014;21(4): T67-T78.
Pretorius E, Arlt W, Storbeck K. A new dawn for androgens: novel lessons from 11-oxygenated C19 steroids Mol. Cell Endocrinol. 2017;441:76-85.
Rizner T, Lin H, Peehl D, Steckelbroeck S, Bauman D, Penning T. Human type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2) and androgen metabolism in prostate cells. Endocrinology. 2003;144(7):2922-32.
Schiffer L, Kempegowda P, Arlt W, O`Reilly M. Mechanisms in endocrinology: The sexually dimorphic role of androgens in human metabolic disease. Eur J Endocrinol. 2017;177(3):R125-R143.
Sharifi N, Auchus R. Steroid biosynthesis and prostate cancer. Steroids. 2012;77(7):719-26.
Shin B, Hwang E, Im C, Kim S, Jung S, Kang T. Is a decreased serum testosterone level a risk factor for prostate cancer? A cohort study of Korean men. Korean J Urol. 2010;51(12): 819-823.
Song W, Khera M. Physiological normal levels of androgen inhibit proliferation of prostate cancer cells in vitro. Asian J Andrology. 2014;16:864-868.
Stanbrough M, Bubley G, Ross K, Golub T, Rubin M, Penning T, Febbo P, Balk S. Increased Expression of Genes Converting Adrenal Androgens to Testosterone in Androgen-Independent Prostate Cancer. Cancer Res 2006;66:(5).
Stattin P, Lumme S, Tenkanen L, Alfthan H, Jellum E, Hallmans G, Thoresen S, Hakulinen T, Luostarinen T, Lehtinen M, Dillner J, Stenman U, Hakama M. High levels of circulating testosterone are not associated with increased prostate cancer risk: a pooled prospective study. Int J Cancer. 2004;108(3):418-24
Weng H, Li S, Huang J, He Z, Meng X, Cao Y et al. Androgen receptor gene polymorphisms and risk of prostate cancer: a meta-analysis. Sci Rep. 2017;7:40554.
Yoo S, Pettersson A, Jordahl K, Lis R, Lindstrom S, Meisner A, et al. Androgen receptor CAG repeat polymorphism and risk of tmprss2:erg positive prostate cancer. Cancer Epidemiol Biomarkers Prev. 2014;23(10):2027-2031.
