Horm Metab Res 2015; 47(02): 119-124
DOI: 10.1055/s-0034-1374631
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

Gene Expression of Androgen Metabolising Enzymes in Benign and Malignant Prostatic Tissues

E. P. Khvostova
1   Institute of Molecular Biology and Biophysics, Siberian Branch of the Russian Academy of Medical Sciences, Novosibirsk, Russia
2   Novosibirsk State University, Novosibirsk, Russia
,
A. A. Otpuschennikov
3   Central Clinical Hospital Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russia
,
V. O. Pustylnyak
1   Institute of Molecular Biology and Biophysics, Siberian Branch of the Russian Academy of Medical Sciences, Novosibirsk, Russia
2   Novosibirsk State University, Novosibirsk, Russia
,
L. F. Gulyaeva
1   Institute of Molecular Biology and Biophysics, Siberian Branch of the Russian Academy of Medical Sciences, Novosibirsk, Russia
2   Novosibirsk State University, Novosibirsk, Russia
› Author Affiliations
Further Information

Publication History

received 23 January 2014

accepted 02 April 2014

Publication Date:
08 May 2014 (online)

Abstract

Benign prostatic hyperplasia (BPH) as well as prostate cancer (CaP) are prevalent in the aging male population, and both the diseases display androgen-dependence when the circulating testosterone from the gonads decreases. This suggests that the local or intracrine production of androgens may drive these diseases. Both diseases are dependent on the conversion of androgen by the epithelial compartment to the ligand with higher affinity and can be treated by blocking synthesis of this androgen metabolite. For this approach to be effective, a detailed knowledge of androgen biosynthesis in both disease states is required. The aim of the present study was to investigate the gene expression levels of androgen metabolising enzymes in BPH compared to normal adjacent prostate tissues and CaP. Expression of the genes HSD3B1, HSD17B3, and SRD5A2 was significantly increased in BPH tissues compared to normal adjacent prostate tissues. In contrast to BPH, CaP demonstrated significant decrease in the expression of HSD17B3, AKR1C2, and SRD5A2 compared to normal adjacent prostate tissues. HSD17B2 expression was significantly decreased in all samples. Moreover, HSD3B1 and SRD5A2 mRNA levels were upregulated in BPH compared with CaP. These results suggest that a change in androgen metabolism may be an important step in the pathogenesis of BPH, leading to increased cell proliferation due to in situ androgen synthesis. These features can be used to develop differential treatment strategies for BPH. HSD3B1 and SRD5A2 could be used as therapeutic target for BPH.

Equal contribution


Supporting Information

 
  • References

  • 1 Claessens F, Denayer S, Van Tilborgh N, Kerkhofs S, Helsen C, Haelens A. Diverse roles of androgen receptor (AR) domains in AR-mediated signaling. Nucl Recept Signal 2008; 6: e008
  • 2 Moon J, Jin WJ, Kwak J, Kim H, Yun M, Kim J, Park S, Kim K. Androgen stimulates glycolysis for de novo lipid synthesis by increasing the activities of hexokinase 2 and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 in prostate cancer cells. Biochem 2011; 433: 225-233
  • 3 Li J, Ding Z, Wang Z, Lu JF, Maity SN, Navone NM, Logothetis CJ, Mills GB, Kim J. Androgen regulation of 5α-reductase isoenzymes in prostate cancer: implications for prostate cancer prevention. PLoS One 2011; 6: e28840
  • 4 Sharifi N. The 5α-androstanedione pathway to dihydrotestosterone in castration-resistant prostate cancer. J Investig Med 2012; 60: 504-507
  • 5 Bauman DR, Steckelbroeck S, Peehl DM, Penning TM. Transcript profiling of the androgen signal in normal prostate, benign prostatic hyperplasia, and prostate cancer. Endocrinology 2006; 147: 5806-5816
  • 6 Twiddy A, Leon C, Wasan K. Cholesterol as a potential target for castration-resistant prostate cancer. Pharm Res 2011; 28: 423-437
  • 7 Freeman M, Solomon K. Cholesterol and prostate cancer. J Cell Biochem 2004; 91: 54-69
  • 8 Miller W, Auchus R. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocr Rev 2011; 32: 81-151
  • 9 Castagnetta LA, Carruba G, Traina A, Granata OM, Markus M, Pavone-Macaluso M, Blomquist CH, Adamski J. Expression of different 17beta-hydroxysteroid dehydrogenase types and their activities in human prostate cancer cells. Endocrinology 1997; 138: 4876-4882
  • 10 Penning TM. New frontiers in androgen biosynthesis and metabolism. Cur Opin Endocrinol Diabetes Obes 2010; 17: 233-239
  • 11 Dozmorov M, Azzarello J, Wren J, Fung K, Yang Q, Davis J, Hurst R, Culkin D, Penning T, Lin H. Elevated AKR1C3 expression promotes prostate cancer cell survival and prostate cell-mediated endothelial cell tube formation: implications for prostate cancer progression. BMC Cancer 2010; 10: 672
  • 12 Li J, Ding Z, Wang Z, Lu J, Maity S, Navone N, Logothetis C, Mills G. Androgen regulation of 5α-reductase isoenzymes in prostate cancer: implications for prostate cancer prevention. PLoS One 2011; 6: e28840
  • 13 Hu D, Mackenzie P. Forkhead box protein A1 regulates UDP-glucuronosyltransferase 2B15 gene transcription in LNCaP prostate cancer cells. Drug Metab Dispos 2010; 38: 2105-2109
  • 14 Wako K, Kawasaki T, Yamana K, Suzuki K, Jiang S, Umezu H, Nishiyama T, Takahashi K, Hamakubo T, Kodama T, Naito M. Expression of androgen receptor through androgen-converting enzymes is associated with biological aggressiveness in prostate cancer. J Clin Pathol 2007; 61: 448-454
  • 15 Geller J, Albert J, Loza D, Geller S, Stoeltzing W, de la Vega D. DHT concentrations in human prostate cancer tissue. Clin Endocrinol Metab 1978; 46: 440-404
  • 16 Montgomery R, Mostaghel E, Vessella R, Hess D, Kalhorn T, Higano C, True L, Nelson P. Maintenance of intratumoral androgens in metastatic prostate cancer: a mechanism for castration-resistant tumor growth. Cancer Res 2008; 68: 4447-4454
  • 17 Chang B, Zheng S, Hawkins G, Isaacs S, Wiley K, Turner A, Carpten J, Bleecker E, Walsh P, Trent J, Meyers D, Isaacs W, Xu J. Joint Effect of HSD3B1 and HSD3B2 genes is associated with hereditary and sporadic prostate cancer susceptibility. Cancer Res 2002; 62: 1784-1789
  • 18 Ho SM, Lee MT, Lam HM, Leung YK. Estrogens and prostate cancer: etiology, mediators, prevention, and management. Endocrinol Metab Clin North Am 2011; 40: 591-614
  • 19 Ho CK, Nanda J, Chapman KE, Habib FK. Oestrogen and benign prostatic hyperplasia: effects on stromal cell proliferation and local formation from androgen. J Endocrinol 2008; 197: 483-491
  • 20 Cai C, Balk S. Intratumoral Androgen Biosynthesis in Prostate Cancer Pathogenesis and Response to Therapy. Endocr Relat Cancer 2011; 18: 175-182
  • 21 Almeida J, Conley AJ, Mathewson L, Ball BA. Expression of steroidogenic enzymes during equine testicular development. Reproduction 2011; 141: 841-848
  • 22 Chang KH, Li R, Papari-Zareei M, Watumull L, Zhao YD, Auchus RJ, Sharifi N. Dihydrotestosterone synthesis bypasses testosterone to drive castration-resistant prostate cancer. Proc Natl Acad Sci USA 2011; 108: 13728-13733
  • 23 Steinkamp M, O’Mahony O, Brogley M, Rehman H, Lapensee E, Dhanasekaran S, Hofer M, Kuefer R, Chinnaiyan A, Rubin M, Pienta K, Robins D. Treatment-dependent androgen receptor mutations in prostate cancer exploit multiple mechanisms to evade therapy. Cancer Res 2009; 69: 4434-4442
  • 24 Ji Q, Chang L, Stanczyk FZ, Ookhtens M, Sherrod A, Stolz A. Impaired dihydrotestosterone catabolism in human prostate cancer: critical role of AKR1C2 as a pre-receptor regulator of androgen receptor signaling. Cancer Res 2007; 67: 1361-1369
  • 25 Pfeiffer MJ, Smit FP, Sedelaar JP, Schalken JA. Steroidogenic enzymes and stem cell markers are upregulated during androgen deprivation in prostate cancer. Mol Med 2011; 17: 657-664
  • 26 Elo JP, Akinola LA, Poutanen M, Vihko P, Kyllonen AP, Lukkarinen O, Vihko R. Characterization of 17 beta-hydroxysteroid dehydrogenase isoenzyme expression in benign and malignant human prostate. Int J Cancer 1996; 66: 37-41