Current Evidence for the Involvement of Hypogonadism and Modulation of Steroid Receptors in Prostate Carcinoma

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Published Jun 26, 2023
DOI: https://doi.org/10.18103/mra.v11i6.3895

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Main Article Content

Olayiwola Akanji Popoola
Clinical Chemistry and Molecular Diagnostic Unit, Department of Medical Laboratory Science, Faculty of Basic Medical Sciences, College of Medicine of the University of Lagos, Idi-Araba, Lagos, Nigeria. ; Centre for Genomics of Non-communicable Diseases and Personalized Healthcare, D. K. Olukoya Central Research Laboratory, University of Lagos, Akoka, Lagos, Nigeria.
Titilola Aderonke Samuel
Centre for Genomics of Non-communicable Diseases and Personalized Healthcare, D. K. Olukoya Central Research Laboratory, University of Lagos, Akoka, Lagos, Nigeria. ; Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine of the University of Lagos, Idi-Araba, Lagos, Nigeria.
Mayowa Popoola
Clinical Chemistry and Molecular Diagnostic Unit, Department of Medical Laboratory Science, Faculty of Basic Medical Sciences, College of Medicine of the University of Lagos, Idi-Araba, Lagos, Nigeria.
Simisola Akinsola
Clinical Chemistry and Molecular Diagnostic Unit, Department of Medical Laboratory Science, Faculty of Basic Medical Sciences, College of Medicine of the University of Lagos, Idi-Araba, Lagos, Nigeria.
Olubunmi Magbagbeola
Centre for Genomics of Non-communicable Diseases and Personalized Healthcare, D. K. Olukoya Central Research Laboratory, University of Lagos, Akoka, Lagos, Nigeria.; Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine of the University of Lagos, Idi-Araba, Lagos, Nigeria.
Oluyemi Akinloye
Clinical Chemistry and Molecular Diagnostic Unit, Department of Medical Laboratory Science, Faculty of Basic Medical Sciences, College of Medicine of the University of Lagos, Idi-Araba, Lagos, Nigeria. ; Centre for Genomics of Non-communicable Diseases and Personalized Healthcare, D. K. Olukoya Central Research Laboratory, University of Lagos, Akoka, Lagos, Nigeria.

Abstract

Prostate cancer (PCa) is the most prevalent cancer in the Nigerian male population, similar to other black populations. It is postulated that exposure to endogenous or environmental steroids prompts prostatic mediated changes via steroid receptors as well as a decrease in the androgen/estrogen ratio and aging. Thereby contributing to prostatic carcinogenesis and disease progression. This study is aimed to determine the plasma levels of testosterone, 17β-estradiol as well as the pattern of expression of steroid receptors in subjects with prostate cancer, benign prostatic hyperplasia, and controls. Study participants are made up of a total of 195 consented volunteers consisting of 65 Prostate cancer (PCa) and 65 benign prostatic hyperplasia (BPH) treatment naïve participants and 65 apparently healthy subjects as controls. Anthropometric data were measured using standard methods and biochemical parameters determined by enzyme-linked immunosorbent assay (ELISA). The gene expression is quantified by Real-Time PCR with PerfeCTa SYBR Green SuperMix  on CFX96 Bio-Rad, USA. The results of this study showed increased levels of 17β-estradiol, total androgen receptor (AR) and estrogen receptor-beta (Erβ) in prostate cancer participants compared with controls (P<0.05). A Significant reduction in plasma levels of testosterone in prostate cancer subjects compared with BPH and controls was observed (P<0.001). The plasma levels of androgen receptors were significantly increased in PCa and BPH participants (p<0.05). We observed a positive correlation between ERβ levels and PSA levels in the PCa group (r=0.32, p=0.02). There was a differential expression of AR, ESR1 and ESR2 in the studied group. This study shows hypogonadism and an increased 17β-estradiol, ERβ, and AR levels in subjects with prostate cancer. This data suggests that modulation of these hormones and their receptors may be associated with initiation and progression of prostate cancer and could be valuable in the interpretation of PSA kinetics and stratification of cases after screening.

Keywords: Prostate Cancer, Benign Prostatic Hyperplasia, Androgen Receptor, Hypogonadism 17β-estradiol, Oestrogen Receptor-β

Article Details

How to Cite
POPOOLA, Olayiwola Akanji et al. Current Evidence for the Involvement of Hypogonadism and Modulation of Steroid Receptors in Prostate Carcinoma. Medical Research Archives, [S.l.], v. 11, n. 6, june 2023. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/3895>. Date accessed: 21 nov. 2024. doi: https://doi.org/10.18103/mra.v11i6.3895.
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Issue
Vol 11 No 6 (2023): June Issue, Vol.11, Issue 6
Section
Research Articles

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References

1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA: A Cancer Journal for Clinicians. 2013;63(1):11-30. doi:10.3322/caac.21166.
2. Nelles JL, Hu WY, Prins GS. Estrogen action and prostate cancer. Expert Rev Endocrinol Metab. 2011;6(3):437-451. doi:10.1586/eem.11.20.
3. Wibowo E, Schellhammer P, Wassersug RJ. Role of estrogen in normal male function: Clinical implications for patients with prostate cancer on androgen deprivation therapy. Journal of Urology. 2011;185(1):17-23. doi:10.1016/j.juro.2010.08.094
4. Watts EL, Appleby PN, Perez-Cornago A, Bueno-de-Mesquita HB, Chan JM, Chen C, Cohn AB, Cook MB, Flicker L, Freedman ND, Giles GG, Giovannucci E, Gislefoss RE, Hankey GJ, Kaaks R, Knekt P, Kolonel LN, Kubo T, Marchand LL, Luben RN, Luostarinen T, Männistö S, Metter EJ, Mikami K, Milne RL, Ozasa K, Platz EA, Quirós JR, Rissanen H, Sawada N, Stampfer M, Stanczyk FZ, Stattin P, Tamakoshi A, Tangen CM, Thompson IM, Tsilidis KK, Tsugane S, Ursin G, Vatten L, Weiss NS, Yeap BB, Allen NE, Key TJ, Travis RC. Low Free Testosterone and Prostate Cancer Risk: A Collaborative Analysis of 20 Prospective Studies. European Urology. 2018; 74 (5) 585-594.
5. Christoforou P, Christopoulos PF, Koutsilieris M. The Role of Estrogen Receptor β in Prostate Cancer. Molecular Medicine. 2014;20(1):427-34.
6. Fuentes N, Silveyra P. Estrogen receptor signaling mechanisms. Adv Protein Chem Struct Biol. 2019;116:135-170. doi:10.1016/bs.apcsb.2019.01.001.
7. Yeh CR, Da J, Song W, Fazili A, Yeh S. Estrogen receptors in prostate development and cancer. Am J Clin Exp Urol. 2014;2(2):161-168. Published 2014 Jul 12.
8. Russo J, Russo IH. The role of estrogen in breast cancer. Molecular Basis of Breast Cancer. 2004:89-135. doi:10.1007/978-3-642-18736-0_4
9. Spornraft, M., Kirchner, B., Haase, B., Benes, V., Pfaffl, M. W., and Riedmaier, I. (2014). Optimization of extraction of circulating RNAs from plasma—enabling small RNA sequencing. PloS one, 9(9), e107259. https://doi.org/10.1371/journal.pone.0107259.
10. Mohammadien, H. A., Hussein, M. T., and El-Sokkary, R. T. (2013). Effects of exposure to flour dust on respiratory symptoms and pulmonary function of mill workers. Egyptian Journal of Chest Diseases and Tuberculosis, 62(4), 745–753. https://doi.org/10.1016/J.EJCDT.2013.09.007.
11. Crawford ED, Heidenreich A, Lawrentschuk N, et al. Androgen-targeted therapy in men with prostate cancer: evolving practice and future considerations. Prostate Cancer Prostatic Dis. 2019;22(1):24-38. doi:10.1038/s41391-018-0079-0.
12. Rove KO, Crawford ED, Perachino M, et al. Maximal testosterone suppression in prostate cancer--free vs total testosterone. Urology. 2014;83(6):1217-1222. doi:10.1016/j.urology.2014.02.001.
13. Zeegers MPA, Jellema A, Ostrer H. Empiric risk of prostate carcinoma for relatives of patients with prostate carcinoma. Cancer. 2003;97(8):1894-1903. doi:10.1002/cncr.11262
14. Nuttall FQ. Body Mass Index: Obesity, BMI, and Health: A Critical Review. Nutr Today. 2015;50(3):117-128. doi:10.1097/NT.0000000000000092.
15. Arayombo BE, Ojoawo AO , Akinola OT and Adepoju F (2019) Anthropometric variables evaluation in prediction of prostate cancer; International Journal of Medical Reviews and Case Report. 3(12): 813-818. Doi: 10.5455/IJMRCR.prediction-prostate-cancer.
16. Esfahlan RJ, Zarghami N, Esfahlan AJ, Mollazadeh M, Nejati K, Nasiri M. The Possible Impact of Obesity on Androgen, Progesterone and Estrogen Receptors (ERα and ERβ) Gene Expression in Breast Cancer Patients. Breast Cancer (Auckl). 2011;5:227-237. doi:10.4137/BCBCR.S7707.
17. Di Zazzo E, Galasso G, Giovannelli P, Di Donato M, Castoria G. Estrogens and Their Receptors in Prostate Cancer: Therapeutic Implications. Front Oncol. 2018;8:2. Published 2018 Jan 18. doi:10.3389/fonc.2018.00002.
18. Michaud JE, Billups KL, Partin AW. Testosterone and prostate cancer: an evidence-based review of pathogenesis and oncologic risk. Ther Adv Urol. 2015;7(6):378-387. doi:10.1177/1756287215597633.
19. Usoro AJ, Obot AS, Ekaidem IS, Akaiso OE, Udoh AE, Akinloye O. Serum testosterone, 17β-estradiol and PSA levels in subjects with prostate disorders. Indian Journal of Clinical Biochemistry. 2014;30(1):59-65. doi:10.1007/s12291-013-0411-3.
20. Ferro M, Lucarelli G, Bruzzese D, Di Lorenzo G, Perdonà S, Autorino R, Cantiello F, La Rocca R, Busetto GM, Cimmino A, Buonerba C, Battaglia M, Damiano R, De Cobelli O, Mirone V and Terracciano, D. (2017). Low serum total testosterone level as a predictor of upstaging and upgrading in low-risk prostate cancer patients meeting the inclusion criteria for active surveillance. Oncotarget. 8 (11), 18424 – 18434. https://doi.org/10.18632/oncotarget.12906.
21. Xu P, Choi E, White K, Yafi FA. Low testosterone in male cancer patients and survivors. Sexual Medicine Reviews. 2021;9(1):133-142. doi:10.1016/j.sxmr.2020.03.004.
22. Alvarado, L.C (2010) Population Differences in the Testosterone Levels of Young Men are Associated with Prostate Cancer Disparities in Older Men American Journal of Human Biology 22:449–455 (2010)
23. Zhou Y, Otto-Duessel M, He M, Markel S, Synold T, Jones JO. Low systemic testosterone levels induce androgen maintenance in benign rat prostate tissue. Journal of Molecular Endocrinology. 2013;51(1):143-153. doi:10.1530/jme-13-0060.
24. Elzanaty S, Rezanezhad B, Dohle G. Association between Serum Testosterone and PSA Levels in Middle-Aged Healthy Men from the General Population. Current Urology. 2016;10(1):40-4.
25. Urbanucci A, Barfeld SJ, Kytölä V, et al. Androgen Receptor Deregulation Drives Bromodomain-Mediated Chromatin Alterations in Prostate Cancer. Cell Rep. 2017;19(10):2045-2059. doi:10.1016/j.celrep.2017.05.049
26. Weischenfeldt J, Simon R, Feuerbach L, Schlangen K, Weichenhan D, Minner S, Wuttig D, Warnatz HJ, Stehr H, Rausch T (2013). Integrative genomic analyses reveal an androgen-driven somatic alteration landscape in early-onset prostate cancer. Cancer Cell 23 159–170. (doi:10.1016/j.ccr.2013.01.002).
27. Dobbs RW, Malhotra NR, Greenwald DT, Wang AY, Prins GS, Abern MR. Estrogens and prostate cancer. Prostate Cancer and Prostatic Diseases. 2019;22(2):185-9.
28. Ajayi A, Abraham K. Understanding the role of estrogen in the development of benign prostatic hyperplasia. African Journal of Urology. 2018;24(2):93-7.
29. Bonkhoff, H., Berges, R. The evolving role of oestrogens and their receptors in the development and progression of prostate cancer. Eur Urol; 2009; 55: 533–542.
30. Lazari MFM, Lucas TFG, Yasuhara F, Gomes GRO, Siu ER, Royer C, et al. Estrogen receptors and function in the male reproductive system. Arquivos Brasileiros de Endocrinologia & Metabologia. 2009;53.
31. Williams C, DiLeo A, Niv Y, Gustafsson JÅ. Estrogen receptor beta as target for colorectal cancer prevention. Cancer Lett. 2016;372(1):48-56. doi:10.1016/j.canlet.2015.12.009.
32. Mobley JA, Brueggemeier RW. Estrogen receptor-mediated regulation of oxidative stress and DNA damage in breast cancer. Carcinogenesis. 2004;25(1):3-9.
33. Hua H, Zhang H, Kong Q, Jiang Y. Mechanisms for estrogen receptor expression in human cancer. Experimental Hematology & Oncology. 2018;7(1):24.
34. Yao S, Till C, Kristal AR, et al. Serum estrogen levels and prostate cancer risk in the prostate cancer prevention trial: a nested case-control study. Cancer Causes Control. 2011;22(8):1121-1131. doi:10.1007/s10552-011-9787-7.
35. Roddam AW, Allen NE, Appleby P, Key TJ. Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. J Natl Cancer Inst. 2008;100(3):170-183. doi:10.1093/jnci/djm323
36. Ramírez-de-Arellano A, Pereira-Suárez AL, Rico-Fuentes C, López-Pulido EI, Villegas-Pineda JC, Sierra-Diaz E. Distribution and effects of estrogen receptors in prostate cancer: Associated Molecular Mechanisms. Frontiers in Endocrinology. 2022;12. doi:10.3389/fendo.2021.811578
37. Li J, Liu Q and Jiang. Signal Crosstalk and the Role of Estrogen Receptor beta (ERβ) in Prostate Cancer Med Sci Monit 2022; 28:e935599, DOI: 10.12659/MSM.935599.
38. Tong D. Selective estrogen receptor modulators contribute to prostate cancer treatment by regulating the tumor immune microenvironment. Journal for ImmunoTherapy of Cancer. 2022;10(4). doi:10.1136/jitc-2021-002944
39. Migliaccio A, Castoria G, Di Domenico M, Steroid-induced androgen receptor-oestradiol receptor beta-Src complex triggers prostate cancer cell proliferation: EMBO J, 2000; 19(20); 5406-17
40. WHO 2011. Waist Circumference and Waist–Hip Ratio: Report of a WHO Expert Consultation Geneva, 8–11 December 2008. https://apps.who.int/iris/bitstream/handle/10665/44583/9789241501491_eng.pdf;jsessionid=A6C4C56A14ACD6A55241AB42CEB00227?sequence=1 (accessed 03.04.2023)